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)

Insulin infusion improves myocardial blood flow (MBF) in healthy subjects. Until now, the effect of insulin on myocardial perfusion in type 2 diabetic subjects with coronary artery disease (CAD) has been unknown. We studied the effects of insulin on MBF in ischemic regions evaluated by single-photon emission-computed tomography and coronary angiography and in nonischemic regions in 43 subjects (ages 63 +/- 7 years) with type 2 diabetes (HbA(1c) 7.1 +/- 0.9%). MBF was measured at fasting and during a euglycemic-hyperinsulinemic clamp at rest (n = 43) and during adenosine-induced (140 mug . kg(-1) . min(-1) for 7 min) hyperemia (n = 26) using positron emission tomography and (15)O-labeled water. MBF was significantly attenuated in ischemic regions as compared with in nonischemic regions (P < 0.0001) and was increased by insulin as compared with in the fasting state (P < 0.0001). At rest, insulin infusion increased MBF by 13% in ischemic regions (P = 0.043) and 22% in nonischemic regions (P = 0.003). During adenosine infusion, insulin enhanced MBF by 20% (P = 0.018) in ischemic regions and 18% (P = 0.045) in nonischemic regions. In conclusion, insulin infusion improved MBF similarly in ischemic and nonischemic regions in type 2 diabetic subjects with CAD. Consequently, in addition to its metabolic effects, insulin infusion may improve endothelial function and thus increase the threshold for ischemia and partly contribute to the beneficial effects found in clinical trials in these subjects.
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PMID:Insulin improves myocardial blood flow in patients with type 2 diabetes and coronary artery disease. 1644 88

Gastroparesis is the most severe form of gastric neuromuscular dysfunction along a continuum that encompasses gastric visceral hypersensitivity, gastric dysrhythmias, and pylorospasm. Gastroparesis may present with vague dyspepsia symptoms or with vomiting of undigested food and weight loss. A careful history and physical examination may suggest the diagnosis of gastroparesis, but symptoms associated with gastric neuromuscular disorders are non-specific. Gastroparesis in patients with diabetes, particularly type 2 diabetes, is more common than appreciated. If gastroparesis is confirmed, then reversible causes such as mechanical obstruction of stomach and chronic mesenteric ischemia must be excluded. ''Idiopathic'' gastroparesis may follow viral infections or be due to degenerative processes that affect gastric enteric neurons, smooth muscle, and/or interstitial cells of Cajal. An approach to the diagnosis and treatment of gastroparesis and gastric neuromuscular disorders is reviewed including dietary counselling and new medical devices.
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PMID:Gastroparesis and neuromuscular disorders of the stomach. 1648 77

Most patients with type 2 diabetes die from heart disease. Screening for the presence of myocardial ischemia is of clinical importance in the management of this population. The pain response to ischemia can be either absent or blunted in diabetes, resulting in the absence of symptoms or an atypical presentation. Exercise electrocardiogram (ECG) should be the initial test in men who are able to exercise and have a normal resting ECG. Stress cardiac imaging should be the initial test in diabetic men with an abnormal resting ECG or who are not able to exercise. More widespread use of cardiac imaging is probably justified in diabetic women and patients with suspected coronary artery disease. Official guidelines for appropriate and cost-effective cardiac investigation should help physicians manage diabetic patients.
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PMID:Cardiac investigation in patients with diabetes. 1648 59

In long-standing diabetes mellitus, blood flow to essential organs including the retina is reduced owing to macrovascular and/or microvascular changes. Poor glycolytic pathway of glucose metabolism owing to tissue hypoxia caused by ischemia at capillary bed of essential organs produces excessive lactic acid and less of adenosine triphosphate, which lead to poor cellular function. The purpose of the study was to evaluate the relationship between increased anaerobic glycolysis and visual acuity in type 2 diabetes mellitus without retinopathy. Fifty patients of type 2 diabetes mellitus of 10-12 years duration, without retinopathy, constituted the study group. The controls were 50 age-matched healthy persons without diabetes mellitus. Blood lactate level and best-corrected visual acuity (BCVA) were measured in both the groups. The mean blood lactate level was 1.05 mM/l in the control group and 2.32 mM/l in the study group. BCVA of 20/20 (log MAR 0) was seen in 48 (96%) patients of the control group and in 27 (54%) patients of the study group. BCVA of 20/30 (log MAR 0.2) was seen in 23 (46%) patients in the study group and 2 (4%) in the control group. Association of higher blood lactate level with decreased BCVA in the study group was statistically significant (P< 0.001).
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PMID:Relation between increased anaerobic glycolysis and visual acuity in long-standing type 2 diabetes mellitus without retinopathy. 1653 71

The objective of this study was to determine the relationship of sociodemographics; diabetes-related factors, including diabetes-related microvascular complications; cardiac risk factors; and psychological factors with quality of life (QOL). Participants enrolled at three sites in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study were invited to participate in this ancillary study. Questionnaires assessing psychological factors were completed by participants, and the remainder of the data was obtained as part of the DIAD study. Many participants had elevated levels of anxiety (n = 91; 82%), depressive symptoms (n = 16; 14%), anger (n = 38; 34%), and hostility (n = 17; 17%). Results of multivariate analyses conducted for each of the eight domains on the Medical Outcomes Study Short Form-36 and two Diabetes Quality of Life domains demonstrated that in the majority of models (42% to 68% of the variance explained), female sex, peripheral or autonomic neuropathy, physical inactivity, higher body mass index, and the presence of depressive symptoms and anxiety were associated with poorer QOL (p = .0001). These findings demonstrate that anxiety, depressive symptoms, and neuropathy are prevalent in older adults with type 2 diabetes. In addition, potentially important correlations were demonstrated between psychological factors, neuropathy, body mass index, and physical inactivity.
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PMID:The association of psychological factors, physical activity, neuropathy, and quality of life in type 2 diabetes. 1658 98

Previous studies indicate that endothelial nitric oxide synthase (eNOS) function is impaired in diabetes as a result of increased vascular generation of reactive oxygen species. We hypothesized that eNOS gene therapy would augment NO. bioavailability and protect against hepatic ischemia-reperfusion (I-R) injury in type 2 diabetes mellitus. We developed a transgenic (Tg) diabetic mouse in which eNOS is systemically overexpressed. We also examined the effects of hepatic eNOS adenovirus therapy in diabetic mice. Diabetic (db/db) and nondiabetic mice were subjected to hepatic I-R injury. In nondiabetic mice, genetic overexpression of eNOS (both eNOS-Tg and eNOS adenovirus) resulted in hepatoprotection. In contrast, hepatic I-R injury was significantly increased in the db/db eNOS-Tg mouse, as serum alanine aminotransaminase (ALT) levels were increased by 3.3-fold compared with diabetic controls. Similarly, eNOS adenovirus treatment resulted in a 3.2-fold increase in serum ALT levels as compared with diabetic controls. We determined that hepatic eNOS was dysfunctional in the db/db mouse and increased genetic expression of eNOS resulted in greater production of peroxynitrite. Treatment with the eNOS cofactor tetrahydrobiopterin (BH4) or the BH4 precursor sepiapterin resulted in a significant decrease in serum ALT levels following I-R injury. We present clear examples of the protective and injurious nature of NO. therapy in I-R. Our data indicate that eNOS exists in an "uncoupled" state in the setting of diabetes and that "recoupling" of the eNOS enzyme with cofactor therapy is beneficial.
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PMID:eNOS gene therapy exacerbates hepatic ischemia-reperfusion injury in diabetes: a role for eNOS uncoupling. 1676 64

Obesity-related disorders are closely associated with the pathogenesis of cardiovascular disease. Adiponectin is a circulating adipose tissue-derived hormone that is down-regulated in obese individuals. Hypoadiponectinemia has been identified as an independent risk factor for type 2 diabetes, coronary artery disease, and hypertension, and experimental studies show that adiponectin plays a protective role in the development of insulin resistance, atherosclerosis, and inflammation. More recent findings have shown that adiponectin directly affects signaling in myocardial cells and exerts beneficial actions on the heart after pressure overload and ischemia-reperfusion injury. This review focuses on the role of adiponectin in the regulation of myocardial remodeling and acute cardiac injury.
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PMID:Cardioprotection by adiponectin. 1678 46

Modern coronary revascularization therapies, coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI), continue to evolve and are widely applied. However, for patients with mild stable angina, or those who are asymptomatic with angiographically documented coronary artery disease (CAD), no survival benefit or reduction in the incidence of myocardial infarction has been demonstrated with CABG or PCI, except in the case of subgroups with angiographically determined high risk due to extensive multivessel disease with depressed LV function or left main CAD. At the same time, medical therapy continues to advance, with demonstrable benefit in both primary and secondary prevention of atherosclerotic coronary disease events. Patients with type 2 diabetes mellitus, at increased risk for adverse cardiac events, have been shown to benefit from these approaches as well. However, in asymptomatic or mildly symptomatic patients with documented ischemia and angiographically significant CAD, the incremental benefit-or hazard-associated with early revascularization superimposed on aggressive medical and risk factor modification therapies is unknown. We discuss the background and rationale for investigating the impact of early revascularization in patients with diabetes and CAD.
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PMID:Rationale for the revascularization arm of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial. 1681 36

The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is activated by acute increases in the cellular [AMP]/[ATP] ratio. In skeletal and/or cardiac muscle, AMPK activity is increased by stimuli such as exercise, hypoxia, ischemia, and osmotic stress. There are many lines of evidence that increasing AMPK activity in skeletal muscle results in increased rates of glucose transport. Although similar to the effects of insulin to increase glucose transport in muscle, it is clear that the underlying mechanisms for AMPK-mediated glucose transport involve proximal signals that are distinct from that of insulin. Here, we discuss the evidence for AMPK regulation of glucose transport in skeletal and cardiac muscle and describe research investigating putative signaling mechanisms mediating this effect. We also discuss evidence that AMPK may play a role in enhancing muscle and whole body insulin sensitivity for glucose transport under conditions such as exercise, as well as the use of the AMPK activator AICAR to reverse insulin-resistant conditions. The identification of AMPK as a novel glucose transport mediator in skeletal muscle is providing important insights for the treatment and prevention of type 2 diabetes.
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PMID:AMP-activated protein kinase and the regulation of glucose transport. 1682 58

Patients with diabetes, in particular patients with type 2 diabetes, are at a 2- to 4-fold higher risk of cardiovascular mortality compared with their nondiabetic peers. Patients with diabetes are also more likely to have silent ischemia and less likely to survive a myocardial infarction than nondiabetic patients. Recent studies with electron beam computed tomography (EBCT) have shown that subclinical atherosclerosis is common in patients with diabetes, and studies with myocardial perfusion scintigraphy (with single-photon emission computed tomography) or stress echocardiography have demonstrated that between 25% and 50% of asymptomatic diabetic patients have ischemia during exercise or pharmacological stress and that a substantial proportion of these patients go on to develop major cardiovascular events within several years. Clearly, asymptomatic diabetic patients include a subset of individuals at high risk of cardiovascular disease who would benefit from improved risk stratification beyond that possible with risk factor scoring systems alone. Single-photon emission computed tomography, stress echocardiography, and possibly EBCT or multi-slice computed tomography, are emerging as valuable diagnostic tools for identifying asymptomatic diabetic patients who might require early and aggressive intervention to manage their cardiovascular risk.
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PMID:The potential of myocardial perfusion scintigraphy for risk stratification of asymptomatic patients with type 2 diabetes. 1690 45


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