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

Diabetes increases both the incidence of cardiovascular disease and complications of myocardial infarction and heart failure. Studies using diabetic animals have shown that changes in myocardial sodium transporters result in alterations in intracellular sodium (Na(i)) homeostasis. Because the changes in sodium homeostasis can be due to increased entry of Na+ via the electroneutral Na+-K+-2Cl- cotransporter (NKCC), we conducted experiments in acute diabetic hearts to determine if 1) net inward cation flux via NKCC is increased, 2) this cotransporter contributes to a greater increase in Na(i) during ischemia, and 3) inhibition of NKCC limits injury and improves function after ischemia-reperfusion. These issues were investigated in perfused type I diabetic and nondiabetic rat hearts subjected to ischemia and 60 min of reperfusion. A group of diabetic and nondiabetic hearts was perfused with 5 microM of bumetanide, an inhibitor of NKCC. Flux via NKCC, Na(i), and ATP was measured in each group with the use of radiotracer 86Rb, 23Na, and 31P nuclear magnetic resonance spectroscopy, respectively, whereas ischemic injury was assessed by measuring creatine kinase release on reperfusion. Cation flux via NKCC, as measured by 86Rb uptake, was significantly increased in diabetic hearts. Inhibition of NKCC significantly reduced ischemic injury in diabetic hearts, improved functional recovery on reperfusion, attenuated the ischemic rise in Na(i), and conserved ATP during ischemia-reperfusion. Parallel studies in nondiabetic hearts showed that NKCC inhibition was not cardioprotective. These findings demonstrate that flux via NKCC is increased in type I diabetic hearts and that inhibition with bumetanide attenuates changes in Na(i) and ATP during ischemia and protects against ischemic injury. The data suggest a therapeutic role for pharmacological agents that inhibit flux via NKCC in diabetic patients with myocardial ischemia.
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PMID:Protection of ischemic myocardium in diabetics by inhibition of electroneutral Na+-K+-2Cl- cotransporter. 1145 52

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

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

While differences between anterior and inferior acute myocardial infarction have been observed, clinical features of lateral infarction are poorly investigated. However, the impact of gender on clinical course and prognosis after myocardial infarction is not fully understood. Electrocardiographically determined infarct site, demographic and clinical variables were prospectively recorded for 1623 consecutive patients admitted to Clinical Hospital Split between 1990 and 1994 due to a first Q-wave acute myocardial infarction. Anterior infarctions were correlated with a higher prevalence of diabetes (P=4 x 10(-6)) or pulmonary venous congestion (P=2 x 10(-12)); inferior infarctions were correlated with a lower prevalence of hypertension (P=0.001), hypercholesterolemia (P=0.02) or diabetes (P=10(-5)), and a higher prevalence of smoking (P=0.001); lateral infarctions were characterized by a smaller infarction size and lower prevalence of pulmonary congestion (P=0.002). Among men under the age of 50 with inferior infarction there were 90% smokers, which was significantly more than among their gender (P=0.005) or infarct site (P=2 x 10(-5)) counterparts. After adjustment for age and other confounding factors, the prevalence of inferior infarction was higher in men (P=0.002). Increased age (P=0.002), female gender (P=0.0006), anterior site (P=10(-5)), diabetes (P=0.0003), greater creatine kinase-MB fraction level (P=0.001) and pulmonary congestion (P=9 x 10(-6)) were independent predictors of an adverse hospital outcome. Each site of acute myocardial infarction has relatively specific preinfarction and clinical features. Our results suggest a greater importance of vasoconstriction in the pathophysiology of inferior infarction, especially in young male smokers, and greater importance of advanced atherosclerotic process in occurrence of anterior infarction.
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PMID:Acute myocardial infarction: differing preinfarction and clinical features according to infarct site and gender. 1295 51

Rhabdomyolysis is a potentially lethal disorder, characterized by elevated serum concentrations of creatine kinase (CK) due to skeletal muscle injury. In this paper a patient with diabetic ketoacidosis (DKA) is reported who developed rhabdomyolysis (maximum CK level, 37,700 U/L; normal, < 170 U/L), anemia (6.2 g/dL) and thrombocytopenia (16,000/microL). This combination of rhabdomyolysis with anemia and thrombocytopenia has not yet been reported in DKA. The pathogenic mechanism leading to rhabdomyolysis in DKA remains unsettled. From the literature it seems that those patients who develop rhabdomyolysis have very high glucose levels and a high osmolality on admission. Low phosphate levels can play a role as well. The etiology of anemia and thrombocytopenia in our patient remains obscure. Intravascular hemolysis could not be demonstrated but intramedullar hemolysis, due to osmolar shift or hypophosphatemia, cannot be excluded. A review of the literature data revealed that rhabdomyolysis is not so uncommon in DKA. However, to obtain incidence data in children, prospective studies are necessary.
Pediatr Diabetes 2003 Mar
PMID:Rhabdomyolysis in diabetic ketoacidosis. 1465 21

Large-scale intervention trials demonstrate that treatment with statins, the most effective lipid lowering drug class, significantly reduces the risk of coronary heart disease events. Recent evidence suggests that more aggressive LDL cholesterol lowering with newly developed statins may provide greater clinical benefit, even in individuals with moderately elevated serum cholesterol levels. There is increasing evidence that statins exert a myriad of other beneficial pleiotropic effects on the vascular wall, thus altering the course of atherosclerotic disease. In the long-term treatment, non-life-threatening side effects may occur in up to 15% of patients receiving one statin. Significant elevations in the activity of serum aminotransferase and creatine kinase alone or in combination with muscle pain in statin-treated patients should be taken seriously. The combination of the statins with gemfibrozil results in higher rates of drug toxicity. Reports show possible adverse effects of statins on nervous system function including mood alterations, however, statins have also been associated with improvement in central nervous system disorders. Special attention must be paid to the tolerability of the statins in children, elderly and transplant patients. Future clinical studies and surveillance information will warrant long term safety of each member of this class of lipid-lowering agents. New classes of patients with diabetes, metabolic syndrome and renal diseases may have clinical benefits from statins. New upcoming clinical trials will address the fundamental question of whether statin treatment can protect from the natural history of atherosclerotic-related diseases. This will require a more prolonged follow-up (i.e., 10 to 15 years). Finally, the basic understanding of newer pathogenic mechanisms involving the effects of statins on angiogenesis and the nitric oxide pathway should be explored in the clinical setting as well as the study of pathogenic mechanisms by which statins can affect plaque instability.
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PMID:Statin treatment and the natural history of atherosclerotic-related diseases: pathogenic mechanisms and the risk-benefit profile. 1496 3


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