Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The existence of a distinct diabetic cardiomyopathy, characterized by a raised left ventricular mass, has previously been suggested. However, as diabetes mellitus is associated with both left ventricular hypertrophy and hypertension a confounding effect of raised blood pressure in diabetic patients has to be considered. In the present cross-sectional study an echocardiographical examination was performed as part of a health screening survey in 582 males, aged 70 years. After the exclusion of subjects with coronary heart disease or those on regular antihypertensive treatment, 30 normotensive subjects with diabetes were compared with 10 subjects with non-insulin-dependent diabetes (NIDDM) and a diastolic blood pressure 90 mm Hg or more and 203 normotensive control subjects with normal glucose tolerance. Both groups with NIDDM showed a significantly increased left atrial diameter (4.4 +/- 0.7 vs 4.0 +/- 0.5 cm, p < 0.05) and an increased atrial component in diastole (A-wave, p < 0.01) compared to the control subjects. Left ventricular mass was, however, only marginally and not significantly elevated in the diabetic subjects when compared to the healthy control subjects (133 +/- 19 and 133 +/- 28 vs 128 +/- 25 g/m2). Only in the subjects with concomitant diabetes and a raised blood pressure was the intraventricular septum significantly enlarged (p < 0.05). Thus, in the present sample no distinct diabetic cardiomyopathy with an increased left ventricular mass, independent of the influence of hypertension could be detected. The myocardial alterations in these diabetic males were restricted to an increased left atrial size and an impaired diastolic function.
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PMID:Relationship between diastolic hypertension and myocardial morphology and function in elderly males with diabetes mellitus. 896 Aug 49

Recent studies at our institution using positron emission tomography (PET) provide evidence that both myocardial blood flow (MBF) and glucose metabolism may be affected in patients with diabetes mellitus. A retrospective study revealed inadequate myocardial glucose uptake as assessed by 2-[18F]fluoro-2-deoxyglucose (18FDG) in 64% of type I (insulin-dependent diabetes mellitus, IDDM) and 36% of type II (non-insulin-dependent diabetes mellitus, NIDDM) patients. However, a study in 7 patients with IDDM and 9 controls showed that metabolic standardization using hyperinsulinemic-euglycemic clamp is associated with similar myocardial glucose uptake in both groups (0.43 +/- 0.16 vs 0.44 +/- 0.12 micromol/g per min; p = nonsignificant). Furthermore, we studied MBF as assessed by [13N]ammonia in 15 IDDM patients without coronary artery disease. We found an impairment in flow reserve in diabetic patients as compared with a control group of 13 healthy volunteers (2.6 +/- 1.3 vs 4.0 +/- 0.6; p <0.01), which was primarily due to a significantly higher resting MBF (95.3 +/- 27.7 vs 69.1 +/- 8.1 mL/100 g per min; p <0.01). Hyperemic flow during adenosine infusion tended to be lower in diabetics, but was not significantly different (236.3 +/- 105.7 vs 273.0 +/- 26.0 mL/100 g per min; p = nonsignificant). Morphologic and functional abnormalities of the coronary microcirculation have been reported in diabetic animals and humans. Furthermore, there is an ongoing controversy regarding the existence of a specific diabetic cardiomyopathy that is not related to epicardial coronary disease. However, few studies have explored the effect of diabetes, hyperinsulinemia, or hyperglycemia on MBF and glucose metabolism in humans. With PET it is possible to perform comprehensive noninvasive studies of various aspects of cardiac function in patients with diabetes mellitus.
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PMID:Myocardial blood flow and glucose metabolism in diabetes mellitus. 929 61

To gain insight into the pathogenesis of diabetic cardiomyopathy, we investigated cardiac function in terms of the coupling of left ventricular mechanical work and the energetics in Otsuka Long-Evans Tokushima Fatty rats, which are well known as a model of type 2 diabetes mellitus (DM). Neither left ventricular systolic function and mean coronary flow nor coronary flow reserve differed even in late DM rats. The amount of oxygen required for mechanical work and contraction was unaltered, although myosin isozyme was finally transformed from V(1) to V(3). The maximum pacing rate was decreased from 300 to 240 beats/min, and the left ventricular relaxation rate was significantly (P < 0.05) slower only in late DM rats, resulting in decreased oxygen consumption per minute for total Ca(2+) handling in excitation-contraction coupling mainly consumed by sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) without significant changes in basal metabolism or in mitochondrial oxidative phosphorylation. The protein level of SERCA2 in membranes was significantly (P < 0.001) lower in severe DM rats. We conclude that the only lusitropic dysfunction due to the depressed expression of SERCA2 is related to generating diabetic cardiomyopathy even in the present type 2 diabetic rats.
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PMID:Left ventricular diastolic dysfunction in type 2 diabetes mellitus model rats. 1174 57

Cardiovascular disease is the leading cause of death in patients with type 2 diabetes, with more than 77,000 deaths each year. The risk remains high despite normalization of well-known cardiovascular risk factors, and the impact of glycemic control on risk reduction remains controversial. Deleterious changes in fibrinolysis, platelet function, and coagulation secondary to insulin resistance and/or the metabolic derangements of type 2 diabetes have emerged as likely mechanisms underlying increased cardiovascular risk. Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of the fibrinolytic system. Thus, elevated concentrations of PAI-1 promote persistence of clots. Concentrations of PAI-1 are elevated in the blood and vessel walls of patients with type 2 diabetes or other insulin-resistant states. We have hypothesized that increased PAI-1 can create conditions favorable to the evolution of unstable, lipid-laden atherosclerotic coronary plaques, thereby rendering patients with diabetes highly susceptible to rupture of vulnerable plaques and acute coronary syndromes. Therapeutic interventions that may alter this evolution by reducing concentrations of PAI-1 or correct metabolic derangements that promote it are being studied. Antiplatelet therapy has been directed at the increased platelet reactivity characteristic of patients with diabetes. Its use has reduced complications after percutaneous coronary intervention following the onset of unstable angina. Amelioration of diabetic cardiomyopathy by correction of impaired myocardial energy metabolism and limiting the accumulation of advanced glycation end products is being evaluated as well.
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PMID:Effects of glycemic control and other determinants on vascular disease in type 2 diabetes. 1243 58

Diabetic cardiomyopathy is an ill-defined entity. This study was designed to explore the possible association between left ventricular diastolic dysfunction (LVDD) and cardiac autonomic neuropathy (CAN) independently from metabolic control. Three groups of 10 age-matched men each with well-controlled type 2 diabetes were studied: (1) subjects with normal diastolic function, (2) subjects with LVDD characterized by impaired LV relaxation, and (3) subjects with a more severe form of LVDD characterized by a pseudonormalized pattern of LV filling. No subject had evidence of clinical diabetic complications, coronary artery disease (CAD), hypertension, congestive heart failure, or thyroid or overt renal disease, and all had a negative maximal exercise test. LVDD was evaluated by Doppler echocardiographic and CAN was evaluated using spectral analysis of heart rate variability (HRV; time and frequency domains) from 24-hour Holter recordings. Findings showed that the high frequency power (HF: 0.15 to 0.4 Hz) tends to decrease with worsening diastolic function; 5.0 +/- 0.2 ms(2) (mean +/- SE) in group 1, 4.2 +/- 0.3 ms(2) in group 2, and 3.9 +/- 0.4 ms(2) (P =.03) in group 3, respectively, whereas the low frequency power (LF: 0.04 to 0.15 Hz) was similar between groups. In the time domain, the mean squared differences of the successive RR intervals (rMSDD) also showed the same pattern, ie, 31.0 +/- 2.8 ms, 23.8 +/- 1.6 ms, and 21.5 +/- 2.9 ms in groups 1, 2, and 3, respectively (P =.03). The E/A ratio correlated significantly with indices of parasympathetic modulation (HF; r = 0.448, P =.013; rMSDD: r = 0.457, P =.011; pNN50: r = 0.425, P =.019). LVDD and CAN are associated in patients with otherwise uncomplicated well-controlled type 2 diabetes. The parameters defining these 2 abnormalities may serve to better define diabetic cardiomyopathy as a distinct entity and could eventually become useful prognostic indicators as it has been shown in nondiabetic populations.
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PMID:Preclinical diabetic cardiomyopathy: relation of left ventricular diastolic dysfunction to cardiac autonomic neuropathy in men with uncomplicated well-controlled type 2 diabetes. 1289 73

The risk for cardiovascular disease, particularly congestive heart failure, is significantly higher in patients with type 2 diabetes mellitus than in individuals without diabetes. The presence of hyperglycemia has been associated with changes in the myocardium that are characteristic of diabetic cardiomyopathy and heart failure. Furthermore, insulin resistance may be associated with cardiomyopathy, even in the absence of hyperglycemia, and has been linked with cardiovascular remodeling. The association between heart failure and insulin resistance suggests that agents that improve insulin sensitivity, such as the thiazolidinediones (TZDs), are likely to be of cardiovascular benefit in patients with diabetes and heart failure. Although TZDs have beneficial cardiovascular effects in patients with type 2 diabetes, such as reducing blood pressure, improving endothelial function, and exerting potential antiatherosclerotic effects, one must be aware of the potential of these agents to cause edema or weight gain as a result of fluid retention and fat accumulation. These issues are of particular concern in patients with diabetes who have heart failure. However, the glycemic and cardiovascular benefits of TZDs may outweigh the potential problems of weight gain and fluid retention noted in some patients. Thus the risk-benefit ratio of using TZDs in patients who have diabetes and heart failure must be carefully considered in this patient population with comorbid disorders.
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PMID:The patient with diabetes mellitus and heart failure: at-risk issues. 1467 75

Many diabetic patients suffer from a cardiomyopathy that cannot be explained by poor coronary perfusion. Reactive oxygen species (ROS) have been proposed to contribute to this cardiomyopathy. Consistent with this we found evidence for induction of the antioxidant genes for catalase in diabetic OVE26 hearts. To determine whether increased antioxidant protection could reduce diabetic cardiomyopathy, we assessed cardiac morphology and contractility, Ca(2+) handling, malondialdehyde (MDA)-modified proteins, and ROS levels in individual cardiomyocytes isolated from control hearts, OVE26 diabetic hearts, and diabetic hearts overexpressing the antioxidant protein catalase. Diabetic hearts showed damaged mitochondria and myofibrils, reduced myocyte contractility, slowed intracellular Ca(2+) decay, and increased MDA-modified proteins compared with control myocytes. Overexpressing catalase preserved normal cardiac morphology, prevented the contractile defects, and reduced MDA protein modification but did not reverse the slowed Ca(2+) decay induced by diabetes. Additionally, high glucose promoted significantly increased generation of ROS in diabetic cardiomyocytes. Chronic overexpression of catalase or acute in vitro treatment with rotenone, an inhibitor of mitochondrial complex I, or thenoyltrifluoroacetone, an inhibitor of mitochondrial complex II, eliminated excess ROS production in diabetic cardiomyocytes. The structural damage to diabetic mitochondria and the efficacy of mitochondrial inhibitors in reducing ROS suggest that mitochondria are a source of oxidative damage in diabetic cardiomyocytes. We also found that catalase overexpression protected cardiomyocyte contractility in the agouti model of type 2 diabetes. These data show that both type 1 and type 2 diabetes induce damage at the level of individual myocytes, and that this damage occurs through mechanisms utilizing ROS.
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PMID:Catalase protects cardiomyocyte function in models of type 1 and type 2 diabetes. 1511 4

Diabetic cardiomyopathy is characterized by a prominent interstitial fibrosis. Postulated etiologies include microangiopathy, autonomic neuropathy, and metabolic factors. A common root of these pathologies is hyperglycemia or hyperinsulinemia, both of which are prominent in type 2 diabetes mellitus, which has the highest incidence of cardiovascular morbidity and mortality. The relative importance of each factor is a matter of debate; it is likely that both of these factors in addition to the concomitant risk factors seen in diabetics (dyslipidemias, hypertension, obesity, coagulation abnormalities) contribute to the spectrum of myocardial disease in diabetes. A discussion of these contributive pathologies and the hyperglycemia and hyperinsulinemia that underlie them is the subject of this review. Treatment methodologies to control the development of such pathology also are discussed.
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PMID:Preventing heart failure in patients with diabetes. 1533 15

Diabetic cardiomyopathy is a distinct entity in diabetic patients with congestive heart failure, who have no angiographic evidence of significant coronary artery stenosis. The aim of this study was to evaluate left ventricular (LV) function in 24 elderly patients (mean age 67 +/- 2 years) with type 2 diabetes, who were asymptomatic and had no history of hypertension, or coronary or valvular heart disease. LV systolic indices (ejection fraction [EF] and fractional shortening [FS]), diastolic indices (E wave, A wave, E/A ratio, isovolumic relaxation time [IVRT] and deceleration time [DT]) and the myocardial performance index (MPI) were evaluated with echocardiography. Compared to controls (24 age- and gender-matched normal subjects), the E wave was reduced (0.60 +/- 0.10 m/sec vs 0.72 +/- 0.08 m/sec, p < 0.05), the A wave was increased (0.77 +/- 0.07 m/sec vs 0.68 +/- 0.06 m/sec, p < 0.05), the E/A ratio was decreased (0.78 +/- 0.20 vs 1.06 +/- 0.18, p < 0.001) and both IVRT and DT were prolonged (0.115 +/- 0.01 sec vs 0.09 +/- 0.01 sec, p < 0.001 and 0.240 +/- 0.04 sec vs 0.180 +/- 0.03 sec, p < 0.001, respectively). The MPI was significantly increased (0.640 +/- 0.170 vs 0.368 +/- 0.098, p < 0.001). LV diastolic function and the MPI are markedly impaired in asymptomatic elderly patients with type 2 diabetes.
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PMID:Evidence of left ventricular dysfunction in asymptomatic elderly patients with non-insulin-dependent diabetes mellitus. 1537 18

Diabetic cardiomyopathy encompasses the spectrum from subclinical disease to the full-blown syndrome of congestive heart failure. The prevalence of type 2 diabetes mellitus is increasing at an alarming rate in the western world. and with it, the frequency of diabetes-related heart failure. There is at least early suggestion that target-driven, long-term, intensified intervention that is aimed at multiple risk factors in patients who have type 2 diabetes and microalbuminuria may reduce the risk of macrovascular (cardiovascular) and micro-vascular complications by approximately 50%. Thus, it is imperative that patients, particularly those who are at risk for the cardiovascular dysmetabolic syndrome, be screened aggressively for the presence of glucose intolerance and diabetes. When detected, all metabolic and cardio-vascular parameters should be evaluated and treated aggressively to reach currently recommended clinical targets. Such action will result in great benefit for patients by reducing morbidity and mortality and improving quality of life and will reduce the financial burden that is associated with this epidemic disease.
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PMID:Diabetes mellitus and heart failure: basic mechanisms, clinical features, and therapeutic considerations. 1550 23


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