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

A key problem in ischemia-induced impairment of the vascular performance of the diabetic heart is the often-unrecognized cardiac sympathetic dysfunction. Advanced single-photon emission computed tomography (SPECT) and positron emission tomography (PET) using the radiopharmaceuticals, (123)I-metaiodobenzylguanidine ((123)I-MIBG) and (11)C-hydroxyephedrine ((11)C-HED), have shown that dysfunction of cardiac sympathetic nerves is present to a large extent in both type 1 and type 2 diabetes. The pattern of sympathetic disturbances is heterogeneous with a predominant effect in the posterior myocardial region. Furthermore, myocardial blood flow assessment with PET has shown that endothelial-dependent vasodilatation is reduced in proportion to the magnitude of cardiac sympathetic dysfunction. These mechanisms are currently proposed to lead from early changes to advanced impairment of cardiac function in diabetes.
 ...
PMID:Cardiac sympathetic innervation and blood flow regulation of the diabetic heart. 1154 8

As rates of diabetes mellitus and obesity continue to increase, physical activity continues to be a fundamental form of therapy. Exercise influences several aspects of diabetes, including blood glucose concentrations, insulin action and cardiovascular risk factors. Blood glucose concentrations reflect the balance between skeletal muscle uptake and ambient concentrations of both insulin and counterinsulin hormones. Difficulties in predicting the relative impact of these factors can result in either hypoglycemia or hyperglycemia. Despite the variable impact of exercise on blood glucose, exercise consistently improves insulin action and several cardiovascular risk factors. Beyond the acute impact of physical activity, long-term exercise behaviors have been repeatedly associated with decreased rates of type 2 diabetes. While exercise produces many benefits, it is not without risks for patients with diabetes mellitus. In addition to hyperglycemia, from increased hepatic glucose production, insufficient insulin levels can foster ketogenesis from excess concentrations of fatty acids. At the opposite end of the glucose spectrum, hypoglycemia can result from excess glucose uptake due to either increased insulin concentrations, enhanced insulin action or impaired carbohydrate absorption. To decrease the risk for hypoglycemia, insulin doses should be reduced prior to exercise, although some insulin is typically still needed. Although precise risks of exercise on existing diabetic complications have not been well studied, it seems prudent to consider the potential to worsen nephropathy or retinopathy, or to precipitate musculoskeletal injuries. There is more substantive evidence that autonomic neuropathy may predispose patients to arrhythmias. Of clear concern, increased physical activity can precipitate a cardiac event in those with underlying CAD. Recognizing these risks can prompt actions to minimize their impact. Positive actions that are part of exercise programs for diabetic patients emphasize SMBG, foot care and cardiovascular functional assessment. SMBG provides critical information on the impact of exercise and is recommended for all patients before, during and after exercise. More frequent monitoring (and for longer periods following exercise) is recommended for those with hypoglycemia unawareness or those performing high-intensity exercise. Preventing the sequelae of an exercise-induced severe hypoglycemic reaction can be as simple as carrying glucose tablets or gel, a diabetic identification bracelet or card, or exercising with an individual who is aware of the circumstances. In addition to blood glucose concentrations, proper foot care is critical to people with diabetes who exercise and includes considering type of shoe, type of exercise, inspection of skin surfaces and appropriate evaluation and treatment of lesions (calluses and others). Those with severe neuropathy can consider alternatives to weight-bearing exercises. Precipitation of clinical CAD is of great concern for all diabetic patients participating in exercise activities. Although a sufficiently sensitive and specific screening test for coronary disease has not been identified, those planning an exercise program of moderate intensity or greater should be evaluated. Initial cardiac assessment should include exercise testing as well as identifying risk for autonomic neuropathy. In addition to noting maximal heart rate and blood pressure as well as ischemic changes, exercise tolerance testing can identify anginal thresholds and patients with asymptomatic ischemia. Those without symptoms should be counseled regarding target pulse rates to avoid inducing ischemia. Ischemic changes need to be evaluated for either further diagnostic testing or pharmacological intervention. For patients with diabetes mellitus, the overall benefits of exercise are clearly significant. Clinicians and patients must work together to maximize these benefits while minimizing risks for negative consequences. Identifying and preventing potential problems beforehand can reduce adverse outcomes and promote this important approach to healthy living.
 ...
PMID:Exercise and diabetes. 1157 Jan 19

Peripheral nerve involvement is a frequent complication of type 1 and type 2 diabetes, and can induce major disability. Almost all types of clinical or electrophysiological disturbances may be present: mononeuropathy involving cranial nerves or a limb; multiple mononeuropathy; proximal acute radiculopathy; distal, symmetric, sensory polyneuropathy; autonomic neuropathy. Physiopathology intricates probably several mechanisms but metabolic dysregulation and ischemia are mainly involved. Despite numerous controlled clinical trials no treatment has demonstrated efficacy for peripheral neuropathy, excepting the optimization of diabetes equilibrium. However, symptomatic treatments are available, particularly for the management of neuropathic pain.
 ...
PMID:[Diabetic neuropathies]. 1179 22

The glucagon-like peptides (GLP-1 and GLP-2) are proglucagon-derived peptides cosecreted from gut endocrine cells in response to nutrient ingestion. GLP-1 acts as an incretin to lower blood glucose via stimulation of insulin secretion from islet beta cells. GLP-1 also exerts actions independent of insulin secretion, including inhibition of gastric emptying and acid secretion, reduction in food ingestion and glucagon secretion, and stimulation of beta-cell proliferation. Administration of GLP-1 lowers blood glucose and reduces food intake in human subjects with type 2 diabetes. GLP-2 promotes nutrient absorption via expansion of the mucosal epithelium by stimulation of crypt cell proliferation and inhibition of apoptosis in the small intestine. GLP-2 also reduces epithelial permeability, and decreases meal-stimulated gastric acid secretion and gastrointestinal motility. Administration of GLP-2 in the setting of experimental intestinal injury is associated with reduced epithelial damage, decreased bacterial infection, and decreased mortality or gut injury in rodents with chemically induced enteritis, vascular-ischemia reperfusion injury, and dextran sulfate-induced colitis. GLP-2 also attenuates chemotherapy-induced mucositis via inhibition of drug-induced apoptosis in the small and large bowel. GLP-2 improves intestinal adaptation and nutrient absorption in rats after major small bowel resection, and in humans with short bowel syndrome. The actions of GLP-2 are mediated by a distinct GLP-2 receptor expressed on subsets of enteric nerves and enteroendocrine cells in the stomach and small and large intestine. The beneficial actions of GLP-1 and GLP-2 in preclinical and clinical studies of diabetes and intestinal disease, respectively, has fostered interest in the potential therapeutic use of these gut peptides. Nevertheless, the actions of the glucagon-like peptides are limited in duration by enzymatic inactivation via cleavage at the N-terminal penultimate alanine by dipeptidyl peptidase IV (DP IV). Hence, inhibitors of DP IV activity, or DP IV-resistant glucagon-like peptide analogues, may be alternative therapeutic approaches for treatment of human diseases.
 ...
PMID:Biological actions and therapeutic potential of the glucagon-like peptides. 1183 66

In patients with diabetes and coronary artery disease, the potential negative role of sulfonylurea drugs is under intensive investigation. We assessed the effects of treatment with glibenclamide or insulin on the extension of left ventricular myocardial dysfunction induced by acute ischemia. Nineteen consecutive patients with type 2 diabetes and coronary artery disease entered the study. Each patient was randomly assigned to either insulin or glibenclamide therapy. Treatment was crossed over after 12 weeks and maintained for another 12 weeks. At the end of each treatment, left ventricular myocardial function at rest and during dipyridamole infusion was studied by two-dimensional echocardiography under the same conditions of metabolic control. Glibenclamide or insulin treatment did not influence the rest values of left ventricular dimensions, left ventricular ejection fraction (LVEF), or wall motion score index (WMSI). Dipyridamole infusion, in patients receiving glibenclamide treatment, decreased LVEF (43 +/- 7 vs. 37 +/- 12%, P < 0.005) and increased WMSI (1.4 +/- 0.28 vs. 1.98 +/- 0.24, P < 0.001) compared with baseline values; during insulin treatment, LVEF (46 +/- 8 vs. 45 +/- 11%, NS) and WMSI (1.4 +/- 0.29 vs. 1.6 +/- 0.4, NS) did not change significantly. Peak stress LVEF was higher (45 +/- 11 vs. 37 +/- 12%, P < 0.001) and WMSI lower (1.6 +/- 0.4 vs. 1.98 +/- 0.24, P < 0.001) in patients receiving insulin. The results indicate that in patients with type 2 diabetes and coronary artery disease, ischemic myocardial dysfunction induced by dipyridamole infusion is less severe during treatment with insulin than with glibenclamide. Restitution of a preconditioning mechanism in insulin-treated patients may be the potential beneficial mechanism.
 ...
PMID:Effects of treatment with sulfonylurea drugs or insulin on ischemia-induced myocardial dysfunction in type 2 diabetes. 1187 84

This study was conducted to evaluate whether treatment of normal and diabetic rat hearts with rosiglitazone, a high-affinity ligand of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) used for the treatment of type 2 diabetes, improves postischemic functional recovery. The effects of acute rosiglitazone administration were investigated using working hearts isolated from normal rat or rats diabetic for 4 weeks after streptozotocin (STZ) injection. Hearts were subjected to 30 min of normothermic, zero-flow ischemia followed by 30-min reperfusion. Rosiglitazone (1 micromol/l) administered before ischemia had no effect on cardiac function during baseline perfusion, but it significantly improved aortic flow during reperfusion in both normal and diabetic hearts. In a chronic protocol in which rosiglitazone was given by daily gavage (10 micromol/kg body wt) immediately after STZ injection, rosiglitazone also prevented postischemic injury and significantly improved functional recovery. Using Western immunoblotting, it was demonstrated that the acute cardioprotective effect of rosiglitazone is associated with an inhibition of Jun NH(2)-terminal kinase phosphorylation in both normal and diabetic rat hearts. Furthermore, rosiglitazone also inhibited activating protein-1 DNA-binding activity. These data, demonstrating that rosiglitazone limits postischemic injury in isolated hearts, suggest an important function for PPAR-gamma in the heart.
 ...
PMID:Rosiglitazone, a peroxisome proliferator-activated receptor-gamma, inhibits the Jun NH(2)-terminal kinase/activating protein 1 pathway and protects the heart from ischemia/reperfusion injury. 1197 49

Three studies have clearly shown that a prolonged QT dispersion (QTD) is the best predictor of cardiac death in patients with type 2 diabetes mellitus (DM). This was originally believed to be because QTD identified electrical inhomogeneity, but recent data suggests that this is unlikely. The alternative possibility is that QTD is a convenient identifier of hidden but lethal cardiac abnormalities. We explored whether the latter possibility is true by examining exactly what spectrum of cardiac abnormalities, if any, are over-represented in diabetics with a prolonged QTD. Two hundred nineteen patients with type 2 DM who had been first diagnosed with DM 3 to 6 years previously underwent intensive cardiac examinations. Patients with prolonged QTD had a significantly increased incidence of myocardial ischemia and left ventricular (LV) hypertrophy, and to a lesser extent, autonomic dysfunction. The main independent determinant of a prolonged QTD was ischemia, as seen on both ambulatory ST-segment monitoring (p <0.001) and Duke score on treadmill testing (p <0.001). It was also observed that QTD increased progressively as the number of different cardiac abnormalities increased (p <0.001). These studies suggest that QTD is a useful, general prescreening test to select diabetics for more detailed cardiac examinations (especially for ischemia and LV hypertrophy), and that if cardiac examinations were targeted by way of QTD screening, then a high incidence of hidden but treatable cardiac abnormalities could be found.
 ...
PMID:Relation of QT interval dispersion to the number of different cardiac abnormalities in diabetes mellitus. 1220 6

Infrared laser therapy (300 Hz) combined with balneotherapy and patients' education is more effective than standard sanatorium rehabilitation in patients with ischemic heart disease associated with diabetes mellitus type 2. 81.8% patients showed good response manifesting in less frequent anginal attacks, episodes of pain and painless ischemia and lower doses of antianginal drugs. Systolic and diastolic arterial pressure lowered by 18 and 10 mm Hg on the average, respectively. Multimodality rehabilitation of IHD patients with type 2 diabetes mellitus improves hemostasis, carbohydrate and lipid metabolism. Coronary circulation response lasted for 24 weeks.
 ...
PMID:[Use of infrared laser therapy in patients with ischemic heart disease associated with diabetes mellitus type 2 in health resort]. 1238 May 22

The renin-angiotensin system evolved to maintain volume homeostasis and blood pressure and to prevent ischemia during acute volume loss. But in the present age, these mechanisms are redundant, and the clinical significance of angiotensin II results from its pathologic effects, which are mediated by the angiotensin II type 1 (AT(1)) receptor. Activation of AT(1) receptors has been linked to pathologic processes that contribute to atherosclerosis and ischemic events, including oxidative stress, inflammatory processes, low-density lipoprotein cholesterol trafficking, and prothrombotic states. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) program will compare the efficacy of the angiotensin II receptor blocker (ARB) telmisartan, the angiotensin-converting enzyme (ACE) inhibitor ramipril, and combination therapy with telmisartan plus ramipril for reducing cardiovascular risk. The ARB telmisartan is distinguished by its long duration of action, which compares favorably with some other ARBs and conventional antihypertensives. Ramipril was shown in the Heart Outcomes Prevention Evaluation (HOPE) study to reduce the risk for myocardial infarction (MI) and other cardiovascular events in patients at high risk for cardiovascular events but without heart failure or a low ejection fraction. The ONTARGET program consists of 2 randomized, double-blind, multicenter international trials: a principal trial, ONTARGET, and a parallel trial, Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease (TRANSCEND). The treatment arms for the principal ONTARGET study are telmisartan 80 mg, ramipril 10 mg, and combination therapy with telmisartan 80 mg plus ramipril 10 mg; for the parallel study TRANSCEND, the treatment arms are telmisartan 80 mg and placebo. Both trials will assess cardiovascular outcomes in patients at high risk using the same criteria as that of the HOPE study, with a single exception: the TRANSCEND trial will enroll patients who do not tolerate ACE inhibitor treatment. The primary end points in both ONTARGET and TRANSCEND are death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. The secondary end points include newly diagnosed heart failure, revascularization, new-onset type 2 diabetes mellitus, nephropathy, cognitive decrease and dementia, and newly diagnosed atrial fibrillation; these will be used for hypothesis generation.
 ...
PMID:The ongoing telmisartan alone and in combination with ramipril global endpoint trial program. 1278 6

Type 2 diabetes mellitus substantially increases the lifetime risk of both developing and dying from heart failure. While this appears to be explained in part by the well-known association of diabetes with hypertension, dyslipidemia, and coronary atherosclerosis, additional pathophysiologic mechanisms linking type 2 diabetes and heart failure have recently been suggested. These include the potentially adverse effects of hyperglycemia on endothelial function and redox state, effects of excess circulating glucose and fatty acids on cardiomyocyte ultrastructure, intracellular signaling and gene expression, and the possibility that diabetes may impair recruitment of the myocardial insulin-responsive glucose transport system in response to ischemia. Because many of these putative pathophysiologic mechanisms should be amenable to normalization of the diabetic metabolic milieu, strategies designed to more carefully control circulating levels of glucose and fatty acids might conceivably delay or prevent the development of heart failure.
 ...
PMID:Diabetes mellitus and heart failure. 1282 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>