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

The primary objectives of claudication treatment are to reduce cardiovascular mortality and improve walking ability. Patients with claudication have 60% mortality over 10 years, with most deaths due to myocardial infarction and stroke. Aggressive risk-factor modification is required in all these patients, particularly smoking cessation, lipid modification, and treatment of hypertension, diabetes and elevated homocysteine levels. Aspirin, ticlopidine and clopidogrel are all effective in reducing the risk of myocardial infarction, stroke and vascular death, and thus antiplatelet therapy should be considered in all claudicants. Patients with disabling claudication should be considered for therapies that relieve claudication pain and improve exercise performance, the most effective being exercise training and smoking cessation. Pentoxifylline, the only approved claudication drug in the United States, has modest efficacy in improving treadmill exercise performance. Other drugs shown to be of some benefit in patients with claudication include propionyl-L-carnitine, cilostazol and possibly prostaglandin derivatives. Several antiplatelet agents and angiogenic growth factors are also being evaluated for the treatment of claudication.
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PMID:Current and future drug therapies for claudication. 954 77

The effects of orally administered propionyl-L-carnitine on cardiac dysfunction in rats with streptozotocin-induced diabetes were investigated. Wistar male rats were divided into four groups: untreated normal, propionyl-L-carnitine (daily for 4 weeks with 3 g/kg orally) -treated normal, untreated diabetic, propionyl-L-carnitine-treated diabetic. Four weeks after streptozotocin administration, plasma lipid levels were increased and myocardial carnitine content was decreased in untreated diabetic rats. These changes were significantly reversed by the propionyl-L-carnitine treatment. Assessment of cardiac function with isolated perfused working hearts revealed a depression of left ventricular developed pressure as well as both maximum positive and negative dP/dt in untreated diabetic as compared with that in normal hearts. Cardiac function at the higher left atrial filling pressures in the propionyl-L-carnitine-treated diabetic rats was improved significantly compared to that in untreated hearts. The data thus suggest that oral administration of propionyl-L-carnitine can reduce abnormalities of cardiac function, correlated with a significant increase in myocardial carnitine content and improved lipid metabolism in terms of lowered plasma lipids.
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PMID:Effects of propionyl-L-carnitine on cardiac dysfunction in streptozotocin-diabetic rats. 979 35

The effects of acetyl-L-carnitine (ALCAR) on fast axoplasmic transport were studied in cultured dorsal root ganglion (DRG) neurons of diabetic rats. Three-month-old male rats were used 7 days after streptozotocin injection. Neurons obtained from ganglia were cultured with a high concentration of glucose. The amount and the mean velocity of retrogradely transported particles, reduced in the diabetic animal, were transiently recovered by 1 mM ALCAR. The number of particles moving at 0.8-1.2 microm/s, considered to be lysosomes, increased in the velocity distribution. ALCAR did not modify the amount and mean velocity of anterograde particles which were unaffected by diabetes, or of bidirectional particles in neurons of control rats. This study suggests that diabetic neuropathy may be relieved by ALCAR via recovering retrograde axoplasmic transport.
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PMID:Effects of ALCAR on the fast axoplasmic transport in cultured sensory neurons of streptozotocin-induced diabetic rats. 1021 64

This study was designed to study the pathogenesis of cardiomyopathy in animals with longstanding (6 months) diabetes mellitus. Male Wistar rats were made diabetic by the injection of streptozotocin (35 mg/kg) intraperitoneal at 6 months of age. Myocardial contractility was evaluated at 1 year of age by an echocardiogram. Blood was collected at that time to measure blood glucose and hemoglobin A1c as an indicator of metabolic control. Serum carnitine was also measured on the same sample to evaluate the availability of this substance so essential for fatty acid metabolism in the myocardium. Myocardial anatomy was evaluated by both light and electron microscopy after the animals had diabetes for 6 months. It was found that the left ventricular volume was greater at the end of systole and diastole. There was the suggestion of left ventricular fractional shortening and calculated reduced ejection fraction indicating decreased contractility consistent with cardiomyopathy. The hearts had no evidence of coronary vascular occlusion, and the serum cholesterol was normal. Myocardial ultrastructure revealed abnormal-appearing mitochondria consistent with carnitine deficiency. Serum and myocardial carnitine levels in the animals with diabetes and reduced myocardial function were low. Carnitine levels and metabolism could be important in the pathogenesis of diabetic cardiomyopathy.
J Diabetes Complications
PMID:Diabetic cardiomyopathy and carnitine deficiency. 1043 72

Carnitine derivatives may have beneficial effects on cardiac and nerve function in patients with diabetes. The aim of this study was to investigate the effect of acetyl-L-carnitine (ALC) on myocardial sympathetic nervous function as measured with 123I-meta-iodobenzyl guanidine (MIBG) and single-photon emission tomography (SPET) in 19 patients with diabetes (placebo group, n = 6; ALC group, n = 13) at the beginning and at the end of a 1-year randomized, placebo-controlled, double-blind trial. The coefficient of variation for the MIBG analysis was 4%. In patients who were given a placebo, global myocardial MIBG uptake deteriorated during the study (MIBG uptake 1-year follow-up/baseline, 0.86 +/- 0.05, mean +/- standard error of mean), whereas in patients treated with ALC, MIBG uptake did not change significantly (1-year follow-up/baseline, 1.07 +/- 0.08; p = 0.03 between the groups). On the basis of these preliminary data, we conclude that long-term treatment with ALC may be of potential value in preventing the progressive loss of myocardial sympathetic nervous function in patients with diabetes. MIBG-SPET is a sensitive and thus valuable method in assessing the development of myocardial sympathetic nervous dysfunction.
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PMID:Long-term effect of acetyl-L-carnitine on myocardial 123I-MIBG uptake in patients with diabetes. 1075 Jun 38

In this study, the serum total, free and ester carnitine levels in 24 type II diabetes mellitus (DM) patients with complications and 15 type II DM patients with no complications were investigated. The patients were investigated in four groups; the control group included the patients with no complications (group 1), the groups including the patients with retinopathy (group 2), hyperlipidemia (group 3), and neuropathy (group 4). In addition, patients were grouped into two. The first group included 10 patients who took insulin by injection (group 5), and the second group included 29 patients using antidiabetic drugs orally (OAD) (group 6). Free and ester carnitine levels were determined by using Boehringer Manheim UV-enzymatic L-carnitine kit. Statistical analysis results showed that both the plasma total and free carnitine levels of groups 2, 3, and 4 were found to be low when compared to the levels of group 1 (p < 0.05). It was observed that the plasma total and free carnitine levels of group 5 were lower when compared to group 6. No significant difference was observed between the plasma ester carnitine levels of all the groups investigated. As a result of this study, it has been thought that carnitine plays an important role in diabetes mellitus complications.
J Diabetes Complications
PMID:Carnitine deficiency in diabetes mellitus complications. 1076 98

Previous studies have shown that propionyl-L-carnitine (PLC) can exert cardiac antiischemic effects in models of diabetes. In the nonischemic diabetic rat heart, PLC improves ventricular function secondary to stimulation in the oxidation of glucose and palmitate. Whether this increase in the oxidation of these substrates can explain the beneficial effects of PLC in the ischemic reperfused diabetic rat heart has yet to be determined. Diabetes was induced in male Sprague-Dawley rats by an intravenous injection of streptozotocin (60 mg/kg). Treatment was initiated by supplementing the drinking water with propionyl-L-carnitine at the concentration of 1 g/L. After a 6-week treatment period, exogenous substrate oxidation and recovery of mechanical function following ischemia were determined in isolated working hearts. In aerobically perfused diabetic hearts, compared with those of controls, rates of glucose oxidation were lower, but those of palmitate oxidation were similar. Diabetes was also characterized by a pronounced decrease in heart function. Following treatment with by propionyl-L-carnitine, however, there was a marked increase in rates at which glucose and palmitate were oxidized by diabetic hearts and a significant improvement in heart performance. Postischemic recovery of function in diabetic hearts was also improved with PLC. This improvement in contractile function was accompanied by an increase in both glucose and palmitate oxidation. Our findings show that postischemic diabetic rat heart function can be improved following chronic PLC treatment. This beneficial effect of propionyl-L-carnitine can be explained, in part, by an improvement in the oxidation of glucose and palmitate.
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PMID:Propionyl-L-carnitine effects on postischemic recovery of heart function and substrate oxidation in the diabetic rat. 1083 5

Marked reduction in the contents of L-carnitine and acetyl-L-carnitine has been reported in peripheral nerves of rats with experimental diabetes. Since these substances have been claimed to improve a number of signs and symptoms of peripheral neuropathy in controlled clinical trials, this study was aimed at assessing whether nerves from diabetic subjects would also reveal similar decrease in the concentration of L-carnitine and acetyl-L-caritine. To this end, these substances were measured in nerves obtained from 11 patients with diabetic neuropathy, 13 patients with ischemic non-diabetic neuropathy, and 12 normal controls. Nerves from patients with either diabetic neuropathy and ischemic non-diabetic neuropathy showed levels of both carnitines lower than those from normal controls. However, differences among the three groups were not statistically significant, indicating that a reduction in these amino acids probably represents only a co-factor in the development of the variegated clinical picture of human diabetic neuropathy.
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PMID:L-carnitine and acetyl-L-carnitine in human nerves from normal and diabetic subjects. 1097 24

The effects of propionyl-L-carnitine (PLC) on isolated mitochondrial respiration in the ischemic reperfused diabetic heart were studied. Oral PLC treatment of STZ-diabetic rats was initiated for a period of 6 weeks. After treatment, isolated working hearts from diabetic rats were perfused under aerobic conditions then subjected to 25 min of no-flow ischemia followed by 15 min of aerobic reperfusion. At the end of reperfusion, heart mitochondria was isolated using differential centrifugation and respiration measured in the presence of pyruvate, glutamate, and palmitoylcarnitine. Our results indicate that diabetes was characterized by a pronounced decrease in heart function under aerobic conditions as well as during reperfusion following ischemia. Treatment with PLC resulted in a significant improvement in heart function under these conditions. The depressions in state 3 mitochondrial respiration with both pyruvate and glutamate seen in reperfused hearts from diabetic rats were prevented by PLC. State 3 respiration in the presence of palmitoylcarnitine was also improved in the ischemic reperfused diabetic rat heart. Our results show that PLC improves recovery of mechanical function following ischemia in the diabetic rat heart. The beneficial effects of PLC are associated with enhanced mitochondrial oxidation of fuels.
Diabetes Res Clin Pract 2001 Jul
PMID:Effects of propionyl-L-carnitine on isolated mitochondrial function in the reperfused diabetic rat heart. 1137 9

Peripheral arterial disease affects approximately 8-10 million people in the United States. Approximately one-third to one-half of these individuals are symptomatic. The risk factors that contribute to peripheral arterial disease are similar to those associated with other forms of atherosclerosis, including diabetes mellitus, cigarette smoking, hypercholesterolemia, high blood pressure, and hyperhomocysteinemia. Of these, diabetes and cigarette smoking pose the greatest risk for developing peripheral arterial disease. The prognosis of patients with these risk factors is limited because of their greater risks for myocardial infarction, stroke, and cardiovascular death. Cardiovascular mortality correlates inversely with the ankle/brachial index, and the risk of death is greatest in those with the most severe peripheral arterial disease. Treatment regimens to reduce cardiovascular morbidity and mortality in patients with peripheral arterial disease should include risk factor modification and antiplatelet therapy. The cardinal symptoms of peripheral arterial disease include intermittent claudication and rest pain, with the latter being indicative of critical limb ischemia. Therapeutic strategies that focus on improving the patient's quality of life, reducing the severity of claudication, and improving limb viability include supervised exercise training, pharmacotherapy, and revascularization. Two drugs-pentoxifylline and cilostazol-currently are approved by the Food and Drug Administration for the treatment of patients with claudication. Meta-analyses have suggested that, compared with placebo, pentoxifylline improves maximal walking distance by approximately 20-25%. Cilostazol is a phosphodiesterase type 3 inhibitor. In clinical trials, cilostazol has consistently improved maximal walking distance as compared with placebo, with the range of improvement being approximately 40-60%. Drugs that are currently under investigation include propionyl-L-carnitine, vasodilator prostaglandins, L-arginine, and the angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factors.
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PMID:Medical management of peripheral arterial disease. 1140 4


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