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

The role of oxidative stress in streptozotocin (STZ)-induced toxicity and its prevention by a xanthone glucoside, mangiferin was investigated. To induce diabetes mellitus, adult male Wistar rats were injected STZ intravenously at 55 mg/kg body weight. The effect of mangiferin (10 and 20 mg/kg, i.p., 28 days) was investigated in STZ-induced diabetic male rats. Insulin-treated rats (6 U/kg, i.p., 28 days) served as positive control. Diabetic rats given normal saline served as negative control. Normal rats that neither received STZ nor drugs served as normal control. On day 28, the diabetic rats showed significant increase in serum creatine phosphokinase (CPK) and total glycosylated haemoglobin. Kidney revealed tubular degeneration and decreased levels of superoxide dismutase (SOD) and catalase (CAT) with an elevation of malonaldehyde (MDA). Cardiac SOD, CAT and lipid peroxidation were significantly increased. Histopathological findings revealed cardiac hypertrophy with haemorrhages. Analysis of erythrocyte revealed significantly elevated levels of MDA with insignificant decrease in CAT and SOD. Repeated intraperitoneal injections of mangiferin (10 and 20 mg/kg) and insulin (6 U/kg) controlled STZ-induced lipid peroxidation and significantly protected the animals against cardiac as well as renal damage. From the study, it may be concluded that oxidative stress appears to play a major role in STZ-induced cardiac and renal toxicity as is evident from significant inhibition of antioxidant defence mechanism in renal tissue or a compensatory increase in antioxidant defence mechanism in cardiac tissue. Intraperitoneal administration of mangiferin exhibited significant decrease in glycosylated haemoglobin and CPK levels along with the amelioration of oxidative stress that was comparable to insulin treatment.
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PMID:Mangiferin protects the streptozotocin-induced oxidative damage to cardiac and renal tissues in rats. 1209 13

Micronised fenofibrate is a synthetic phenoxy-isobutyric acid derivative (fibric acid derivative) indicated for the treatment of dyslipidaemia. Recently, a new tablet formulation of micronised fenofibrate has become available with greater bioavailability than the older capsule formulation. The micronised fenofibrate 160mg tablet is bioequivalent to the 200mg capsule. The lipid-modifying profile of micronised fenofibrate 160mg (tablet) or 200mg (capsule) once daily is characterised by a decrease in low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels, a marked reduction in plasma triglyceride (TG) levels and an increase in high-density lipoprotein cholesterol (HDL-C) levels. Micronised fenofibrate 200mg (capsule) once daily produced greater improvements in TG and, generally, in HDL-C levels than the hydroxymethylglutaryl coenzyme A reductase inhibitors simvastatin 10 or 20 mg/day, pravastatin 20 mg/day or atorvastatin 10 or 40 mg/day. Combination therapy with micronised fenofibrate 200mg (capsule) once daily plus fluvastatin 20 or 40 mg/day or atorvastatin 40 mg/day was associated with greater reductions from baseline than micronised fenofibrate alone in TC and LDL-C levels. Similar or greater changes in HDL-C and TG levels were seen in combination therapy, compared with monotherapy, recipients. Micronised fenofibrate 200mg (capsule) once daily was associated with significantly greater improvements from baseline in TC, LDL-C, HDL-C and TG levels than placebo in patients with type 2 diabetes mellitus enrolled in the double-blind, randomised Diabetes Atherosclerosis Intervention Study (DAIS) [> or =3 years follow-up]. Moreover, angiography showed micronised fenofibrate was associated with significantly less progression of coronary atherosclerosis than placebo. Micronised fenofibrate has also shown efficacy in patients with metabolic syndrome, patients with HIV infection and protease inhibitor-induced hypertriglyceridaemia and patients with dyslipidaemia secondary to heart transplantation. Micronised fenofibrate was generally well tolerated in clinical trials. The results of a large (n = 9884) 12-week study indicated that gastrointestinal disorders are the most frequent adverse events associated with micronised fenofibrate therapy. Elevations in serum transaminase and creatine phosphokinase levels have been reported rarely with micronised fenofibrate. In conclusion, micronised fenofibrate improves lipid levels in patients with primary dyslipidaemia; the drug has particular efficacy with regards to reducing TG levels and raising HDL-C levels. Micronised fenofibrate is also effective in diabetic dyslipidaemia; as well as improving lipid levels, the drug reduced progression of coronary atherosclerosis in patients with type 2 diabetes mellitus. The results of large ongoing studies (e.g. FIELD with approximately 10 000 patients) will clarify whether the beneficial lipid-modifying effects of micronised fenofibrate result in a reduction in cardiovascular morbidity and mortality.
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PMID:Micronised fenofibrate: an updated review of its clinical efficacy in the management of dyslipidaemia. 1221 67

Skeletal muscle is strongly dependent on oxidative phosphorylation for energy production. Because the insulin resistance of skeletal muscle in type 2 diabetes and obesity entails dysregulation of the oxidation of both carbohydrate and lipid fuels, the current study was undertaken to examine the potential contribution of perturbation of mitochondrial function. Vastus lateralis muscle was obtained by percutaneous biopsy during fasting conditions from lean (n = 10) and obese (n = 10) nondiabetic volunteers and from volunteers with type 2 diabetes (n = 10). The activity of rotenone-sensitive NADH:O(2) oxidoreductase, reflecting the overall activity of the respiratory chain, was measured in a mitochondrial fraction by a novel method based on providing access for NADH to intact mitochondria via alamethicin, a channel-forming antibiotic. Creatine kinase and citrate synthase activities were measured as markers of myocyte and mitochondria content, respectively. Activity of rotenone-sensitive NADH:O(2) oxidoreductase was normalized to creatine kinase activity, as was citrate synthase activity. NADH:O(2) oxidoreductase activity was lowest in type 2 diabetic subjects and highest in the lean volunteers (lean 0.95 +/- 0.17, obese 0.76 +/- 0.30, type 2 diabetes 0.56 +/- 0.14 units/mU creatine kinase; P < 0.005). Also, citrate synthase activity was reduced in type 2 diabetic patients (lean 3.10 +/- 0.74, obese 3.24 +/- 0.82, type 2 diabetes 2.48 +/- 0.47 units/mU creatine kinase; P < 0.005). As measured by electron microscopy, skeletal muscle mitochondria were smaller in type 2 diabetic and obese subjects than in muscle from lean volunteers (P < 0.01). We conclude that there is an impaired bioenergetic capacity of skeletal muscle mitochondria in type 2 diabetes, with some impairment also present in obesity.
Diabetes 2002 Oct
PMID:Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. 1235 31

Little is known of the risk factors of recurrent myocardial infarction (MI) among Japanese patients who have survived their first MI. The risk factors for the second MI were studied in 808 of 1,042 consecutive patients who recovered from an acute MI in Iwakuni National Hospital. Multivariate logistic regression analysis revealed that only 3 of 21 variables measured were closely related with the recurrence of MI during a follow-up period of 3.2 +/- 4.3 years: (1) transient atrial fibrillation (relative risk (RR) 3.16), (2) previous cerebrovascular accident (RR 3.05), and (3) dyslipidemia (RR 2.19). Of the parameters of dyslipidemia, a low ratio of high-density lipoprotein-cholesterol (HDL-C) to low-density lipoprotein-cholesterol (LDL-C) alone indicated subsequent MI. None of age, gender, location of the infarction, hypertension, diabetes mellitus, pulmonary congestion (Killip's class > or = 2), peak serum creatine kinase activity, serum total-cholesterol, HDL- and LDL-cholesterol levels, nor smoking habit on admission was a statistically significant predictor for the second MI. The result suggests that more intensive treatment is needed for patients with the 3 risk factors.
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PMID:Risk factors indicating recurrent myocardial infarction after recovery from acute myocardial infarction. 1238 Oct 77

OBJECTIVE: To investigate the correlation between RFCA catheter cumulative energy and autonomic nerve injury. METHODS: Forty-one patients with paroxysmal supraventricular tachycardia were enrolled, Patients were excluded if they had Diabetes, Hypertension, Congestive Heart Failure or other organic heart disease. HRV and biochemical markers were measured before and after the RFCA. RESULTS: Compared with pre-ablation values,there was significantly decrease in post-ablation low frequency (LF) and high frequency (HF). This was noted in both the septal group (AVNRT and septal pathway) and free wall group (free wall accessory pathway).Post-procedure,the sensitivity of cardiac troponin I(cTnI) for myocardial injury detection was 58.3%, AST was 41.7%. This was significantly higher than other markers(CK:4.2%, CK-MB:10.4%, LDH:20.8%). The post-ablation sensitivity of cTnI was 54.2%, 6.3% and 52.1%at 1 hour, 12 hours, and 24 hours respectively. A significant correlation between cumulative energy and delta HF(r=0.688,P=0.01) or delta LF (r=0.462, P<0.05).was noted in free wall group.(delta HF=pre-ablation HF-post-ablation HF/pre-ablation HF x 100%). There was no significant correlation between biochemical markers and either delta HF or delta LF. CONCLUSION: RFCA induced injury on cardiac autonomic nerves related to both cumulative energy and ablation site,but not size of myocardial injury as determined by cTnI measurement. cTnI is an excellent biochemical marker of myocardial injury.
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PMID:[Radiofrequency catheter ablation autonomic nerve injury] 1259 13

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are associated with skeletal muscle complaints, including clinically important myositis and rhabdomyolysis, mild serum creatine kinase (CK) elevations, myalgia with and without elevated CK levels, muscle weakness, muscle cramps, and persistent myalgia and CK elevations after statin withdrawal. We performed a literature review to provide a clinical summary of statin-associated myopathy and discuss possible mediating mechanisms. We also update the US Food and Drug Administration (FDA) reports on statin-associated rhabdomyolysis. Articles on statin myopathy were identified via a PubMed search through November 2002 and articles on statin clinical trials, case series, and review articles were identified via a PubMed search through January 2003. Adverse event reports of statin-associated rhabdomyolysis were also collected from the FDA MEDWATCH database. The literature review found that reports of muscle problems during statin clinical trials are extremely rare. The FDA MEDWATCH Reporting System lists 3339 cases of statin-associated rhabdomyolysis reported between January 1, 1990, and March 31, 2002. Cerivastatin was the most commonly implicated statin. Few data are available regarding the frequency of less-serious events such as muscle pain and weakness, which may affect 1% to 5% of patients. The risk of rhabdomyolysis and other adverse effects with statin use can be exacerbated by several factors, including compromised hepatic and renal function, hypothyroidism, diabetes, and concomitant medications. Medications such as the fibrate gemfibrozil alter statin metabolism and increase statin plasma concentration. How statins injure skeletal muscle is not clear, although recent evidence suggests that statins reduce the production of small regulatory proteins that are important for myocyte maintenance.
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PMID:Statin-associated myopathy. 1292 63

A subtype of idiopathic type 1 diabetes with a rapid onset and no diabetes-related antibodies has been recently advocated as non-autoimmune fulminant type 1 diabetes. However, it is not definite yet that this subtype is always caused by non-autoimmune mechanism. A 48-year-old man was admitted to our hospital because of high plasma glucose and renal insufficiency. Laboratory findings were as follows: plasma glucose 1052 mg/dL, urinary ketone bodies (+/-), arterial blood pH 7.44, bicarbonate 23.8 mmol/L, base excess 0.3 mmol/L, plasma osmolality 342 mOsm/L, serum creatinine 2.1 mg/dL, blood urea nitrogen 69.7 mg/dL, and serum creatine kinase 1024 IU/L, giving a diagnosis of acute renal failure secondary to rhabdomyolysis associated with diabetes. Urinary C-peptide reactivity was 4.7 microg/day. The level of HbAlc was 7.0%, not so high as compared to that of plasma glucose, indicating an aggravation of diabetes within the recent short period. Antibodies to islet cell antigen, IA-2 and insulin were negative, while those to glutamic acid decarboxylase (GAD) were positive at 13.1 U/mL, which were negative half a year and two years and a half later. Serum amylase level was within normal range at admission, increased to 380 IU/L and normalized in 4 to 5 weeks as serum creatinine lowered. These data are compatible to the diagnosis of fulminant type 1 diabetes. However, the present case is different from others in positive antibodies to GAD at admission that turned to be negative subsequently. Considering our results and others together, further investigations are necessary to clarify whether all cases of fulminant type 1 diabetes are non-autoimmune or some of them are caused by autoimmune mechanism.
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PMID:A case of fulminant type 1 diabetes with transiently positive anti-GAD antibodies. 1280 44

The activities of the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LD), creatine kinase (CK), amylase (AMS) and angiotensin converting enzyme (ACE) have been used to assess the toxic effects of xenobiotics that have hypoglycaemic action in hepatic, pancreatic, renal and muscle tissue. Using a validated experimental model of diabetes mellitus in rats, we ascertained whether this syndrome itself affected the serum activities of these enzymes over a 53-day period. Levels of hepatic enzymes AST, ALT and ALP were higher in the streptozotocin (STZ)-diabetic rats (group D), but were controlled by insulin therapy (group DI). AMS was reduced in group D and unchanged in group DI rats. Proteinuria was detected 1 day after STZ administration and partially controlled by insulin (group DI); its early presence in group D rats, and the lack of any change in serum ACE in this group, indicates that proteinuria is the better marker for microangiopathy. Microscopic examination of liver, kidney, heart and skeletal muscles (soleus and extensor digitorum longus) revealed various alterations in group D rat tissues, which were less pronounced in group DI. The liver, pancreas and kidney tissue-damage was consistent with the altered serum levels of AST, ALT, ALP and AMS and proteinuria. We conclude that: (i) rigorous control is required when these serum-enzyme levels are used as indicators of tissue toxicity in experimental diabetes, and (ii) LD, CK and bilirubin serum levels, which are unaffected by diabetes, can be used when testing effects of xenobiotics on tissues.
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PMID:Temporal response pattern of biochemical analytes in experimental diabetes. 1282 18

Quantitative protein profiling based on in vitro stable isotope labeling, two-dimensional polyacrylamide gel electrophoresis, and mass spectrometry is an accurate and reliable approach to measure simultaneously the relative abundance of many individual proteins within two different samples. In the present study, it was used to define a set of alterations caused by diabetes in heart mitochondria from streptozotocin-treated rats. We demonstrated that the expression of proteins from the myocardial tricarboxylic acid cycle was not altered in diabetes. However, up-regulation of the fatty acid beta-oxidation favored fatty acids over glucose as a source of acetyl CoA for the tricarboxylic acid cycle. Protein levels for several proteins involved in electron transport were modestly decreased. Whether this may depress overall ATP production remains to be established, since the protein level of ATP synthase seems to be unchanged. Other changes include down-regulation of protein levels for creatine kinase, voltage-dependent anion channel 1 (VDAC-1), HSP60, and Grp75. The mitochondria-associated level of albumin was decreased, while the level of catalase was substantially increased. All of the changes were evident as early as 1 week after streptozotocin administration. Taken together, these data point to a rapid and highly coordinated regulation of mitochondrial protein expression that occurs during the heart adaptation to diabetes.
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PMID:Quantitative protein profiling in heart mitochondria from diabetic rats. 1285 9

The efficacy of pravastatin and simvastatin was first shown several years ago in patients with coronary heart disease. Other trials have since been published. In the HPS trial, which studied patients with coronary heart disease, other cardiovascular conditions, or diabetes, simvastatin significantly reduced the risk of death, coronary events and stroke when compared with placebo. In the ALLHAT-LLT trial, in patients with treated hypertension, pravastatin did not reduce overall mortality. In the PROSPER trial, in patients aged over 70 with cardiovascular disease or cardiovascular risk factors, pravastatin reduced the incidence of coronary events relative to placebo, but did not reduce overall mortality. Pharmacovigilance studies suggest there is no difference between these four statins in terms of their potential to cause rhabdomyolysis. Taken together, these trials show that statin use can be extended to patients with levels of LDL-cholesterol over 2.4 mmol/l (0.9 g/l) if they have coronary heart disease (and no hypercholesterolaemia), a history of ischaemic stroke, or lower-limb arterial disease. Statins can also be prescribed for diabetic patients with no signs of cardiovascular disease but whose LDL-cholesterol exceeds 3.4 mmol/l (1.3 g/l). Clinical trial data support the use of pravastatin or simvastatin in these situations, at a dose of 20 or 40 mg daily. Plasma creatine phosphokinase assay should be done if muscle symptoms occur or if the patient has a particular risk of rhabdomyolysis.
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PMID:Statins: new data in secondary prevention and diabetes. Pravastatin and simvastatin are the best-assessed statins. 1290 97


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