Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drugs classified as calcium channel blockers (CHBs) are now among the most frequently prescribed drugs for the treatment of cardiovascular disease. Although the currently available CCBs have major differences in their structural and cardiovascular effects, they share the common property of blocking the transmembrane flow calcium ions through voltage gated L-type channels. These drugs have been approved for the treatment of hypertensive heart disease: they reduce left ventricular hypertrophy and improve its sequelae, such as ventricular dysrhythmias, impaired filling and contractility, and myocardial ischemia. Long-acting CCBs have been shown to reduce mortality and morbidity in elderly patients with systolic hypertension, appear to be extremely useful in patients with cyclosporin-induced hypertension, and can be used as alternatives to ACE inhibitors in patients with hypertension and concomitant diabetes mellitus, renal disease, Raynaud's phenomenon or migraine. Long-acting dihydropyridine have been shown to be effective and safe in the treatment classic angina pectoris and vasospastic angina, supraventricular arrhythmias, particularly reentrant AV-nodal tachycardia, others to be beneficial in patients with congestive heart failure, and all of them have potential for decreasing atherogenesis.
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PMID:[Calcium channel blockers in the treatment of cardiovascular disease]. 1157 40

Insulin resistance and hyperinsulinemia have been observed in over 70% of the nonobese, nondiabetic subjects with essential hypertension (HT). Alpha-1 blockers, ACE-antagonists, long-acting Ca blockers including nifedipine CR, some form of beta-blockers, tilisolor, which is reported to increase blood flow, improve insulin sensitivity when blood pressure is better controlled. Decrease of serum potassium during insulin sensitivity test and intraplatelet free Ca2+ concentration is positively and negatively correlated with insulin sensitivity, respectively. Blood pressure is correlated with insulin resistance, which is also observed in secondary HT. The resistance is correlated with salt sensitivity as well as impaired nocturnal fall of blood pressure. These suggest the possible association of insulin resistance with altered intracellular cation metabolism. Insulin resistance and associated hyperinsulinemia have been observed in effort as well as vasospastic angina pectoris (VSAP), atherothrombotic cerebral infarction, and in ASO without obesity, HT, or diabetes, suggesting the resistance resulting from endothelial dysfunction. Insulin resistance has been observed in heart failure and is correlated with angiotensin II. Resistance is also observed in hypertrophic cardiomyopathy and is partially correlated with TNF-alpha. These results indicate that insulin resistance seem to be multifactorial. An effort to normalize insulin sensitivity is crucial to eliminate multiple risk factors as well as to prevent the progression of atherosclerotic vascular lesions.
J Diabetes Complications
PMID:Multifactorial insulin resistance and clinical impact in hypertension and cardiovascular diseases. 1187 61

Coronary artery calcification (CAC) was assessed by cinefluoroscopy and its extent was scored (CAC score) in 2,163 consecutive patients undergoing coronary angiography, based on the angiographic and clinical data, the patients were categorized into 8 types of coronary artery disease (CAD). The CAC score was lowest in angiographically normal subjects (0.12+/-0.60) and highest in patients with silent myocardial ischemia (14.31+/-8.61). Risk factors for CAC were advanced age, male sex (at age <80 years), hypertension, diabetes mellitus, and a high grade of organic coronary stenosis. The CAC score in patients with acute coronary syndrome (unstable angina+acute myocardial infarction; 5.48+/-7.42) was significantly lower than that in those with chronic CAD (silent ischemia+stable angina; 9.72+/-8.73; p<0.0001), but was still higher than that in normal subjects or those with vasospastic angina (0.92+/-2.88; p<0.0001). The results indicate that CAC is a manifestation of coronary atherosclerosis and its appearance depends on the pathological type of ischemic heart disease. Fixed stenosis with a slow and chronic process tends to be associated with CAC. The clinical implication of extensive CAC in acute coronary syndrome compared with normal subjects should be further investigated.
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PMID:Clinical significance of coronary calcification. 1203 Mar 43

The present study was conducted to evaluate the validity and reproducibility of noninvasive brachial-ankle pulse wave velocity (baPWV) measurements and to examine the alteration of baPWV in patients with coronary artery disease (CAD). Simultaneous recordings of baPWV by a simple, noninvasive method and aortic pulse wave velosity (PWV) using a catheter tip with pressure manometer were performed in 41 patients with CAD, vasospastic angina, or cardiomyopathy. In 32 subjects (15 controls and 17 patients with CAD), baPWV was recorded independently by two observers in a random manner. In 55 subjects (14 controls and 41 patients with CAD), baPWV was recorded twice by a single observer on different days. baPWV were compared among 172 patients with CAD (aged 62 +/- 8 years); 655 age-matched patients without CAD but with hypertension, diabetes mellitus, or dyslipidemia; and 595 age-matched healthy subjects without these risk factors. baPWV correlated well with aortic PWV (r=0.87, p<0.01). Pearson's correlation coefficients of interobserver and intraobserver reproducibility were r=0.98 and r=0.87, respectively. The corresponding coefficients of variation were 8.4% and 10.0%. baPWV were significantly higher in CAD patients than in non-CAD patients with risk factors, for both genders (p<0.01). In addition, baPWV were higher in non-CAD patients with risk factors than in healthy subjects without risk factors. Thus, the validity and reproducibility of baPWV measurements are considerably high, and this method seems to be an acceptable marker reflecting vascular damages. baPWV measured by this simple, noninvasive method is suitable for screening vascular damages in a large population.
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PMID:Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement. 1989 68

The main peripheral sources of 5-hydroxytryptamine (5-HT) are as a neurotransmitter and local hormone in the gastrointestinal tract, and stored in circulating platelets and pulmonary neuroepithelial bodies. 5-HT has been shown to have many possible physiological and pathophysiological roles on the cardiovascular and renal systems. Thus, 5-HT may contribute to valvular heart disease, coronary artery disease, pulmonary hypertension, pulmonary embolism, pre-eclampsia, peripheral vascular disease and diabetic nephropathy. Consequently, modulators of the 5-HT system have diverse clinical potential. For instance, selective 5-HT subtype 3 receptor (5-HT(3)) antagonists may have potential in the treatment of the pain associated with myocardial infarction. MCI-9042 (sarpogrelate) or other 5-HT(2A) antagonists may have clinical potential for the treatment of vasospastic angina, ischaemic heart disease, reperfusion injury and hindlimb ischaemia. Several modulators of 5-HT (5-HT transporter inhibitors, 5-HT(1B) and (2B) antagonists) may have potential alone or in combination in the treatment of pulmonary hypertension. In hypertension, agonists at the 5-HT(7) and antagonists at the 5-HT(2B) may reduce blood pressure, and in diabetes, sarpogrelate may protect against nephropathy.
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PMID:The role of 5-HT on the cardiovascular and renal systems and the clinical potential of 5-HT modulation. 1272 Apr 92

Although patients with medically treated vasospastic angina have a good outcome, few data exist regarding the role of underlying lesion severity associated with or without hyperlipidemia in the prognosis. Therefore, the aim of the present study was to assess the relationship between the long-term outcome of vasospastic angina and the factors influencing its prognosis. A total of 256 patients (219 men, 37 women; mean age, 54.1+/-9.2) who had coronary spasm with or without underlying lesions and were being treated with calcium channel antagonists were enrolled and followed for 13.6+/-3.7 years. Cardiac events consisted of cardiac death and ischemic events, which included acute myocardial infarction and unstable angina. Cox analysis selected coronary artery stenosis (CAS, >/=50%) and risk factors such as age, hypertension, diabetes mellitus, low-density lipoprotein-cholesterol (LDL-C), sex and smoking. There were 19 cases of cardiac death (7.4%) and 58 of ischemic events (22.7%) during the follow-up period. The presence of significant CAS was an independent predictor of event-free survival (hazard ratio (HR) =2.84, 95% confidence interval (CI) =1.79-4.52, p<0.0001). In 193 patients without significant CAS, there were 10 cases of cardiac death (5.2%, p<0.05) and 34 of ischemic events (17.6%, p<0.01). In that group, high LDL-C was the independent predictor of event-free survival (HR = 3.89, 95% CI = 1.20-12.6, p=0.02). Kaplan-Meier survival analysis revealed significantly lower event-free survival in patients with than in those without lesions (p<0.0001 by log-rank test). These results demonstrate that the most important factor for long-term prognosis of vasospastic angina treated with calcium channel antagonists is significant CAS. High LDL-C, which might alter the underlying coronary endothelial function and/or accelerate atherosclerotic lesions, could also contribute to the occurrence of cardiac events, particularly in patients without significant CAS.
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PMID:Lesion severity and hypercholesterolemia determine long-term prognosis of vasospastic angina treated with calcium channel antagonists. 1463 19

In the 1980s, clinical characteristics and long-term prognosis of patients with vasospastic angina (VSA) were investigated; however, they remain to be updated after the introduction of new calcium channel blockers, benidipine and amlodipine, in 1990s. Our patient cohort registered 726 patients with VSA from January 1980 to December 2002. Before and after 1990, 138 and 527 patients were respectively entered in this study with a follow-up rate of 92%. Most of the patients were treated with calcium channel blockers, while benidipine and amlodipine were used in 28% and 21% of them only after 1990. Survival without cardiovascular events (96% versus 96%) at 5 years remained good before and after 1990. The presence of significant coronary stenosis had a negative prognostic impact both before and after 1990, whereas after 1990, diabetes mellitus, smoking, and a history of myocardial infarction became more influential. Among the calcium channel blockers, benidipine showed a better prognosis. These results suggest that in the era of new calcium channel blockers, the prognosis of patients with VSA remains good with more prognostic impact of diabetes mellitus, smoking, and a history of myocardial infarction and that benidipine might have some better prognostic effects.
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PMID:Changing characteristics of patients with vasospastic angina in the era of new calcium channel blockers. 1545 57

ATP-sensitive K+ channels (KATP channels) are present in various tissues, including pancreatic beta-cells, heart, skeletal muscles, vascular smooth muscles, and brain. KATP channels are hetero-octameric proteins composed of inwardly rectifying K+ channel (Kir6.x) and sulfonylurea receptor (SUR) subunits. Different combinations of Kir6.x and SUR subunits comprise KATP channels with distinct electrophysiological and pharmacological properties. Recent studies of genetically engineered mice have provided insight into the physiological and pathophysiological roles of Kir6.x-containing KATP channels. Analysis of Kir6.2 null mice has shown that Kir6.2/SUR1 channels in pancreatic beta-cells and the hypothalamus are essential in glucose-induced insulin secretion and hypoglycemia-induced glucagon secretion, respectively, and that Kir6.2/SUR2 channels are involved in glucose uptake in skeletal muscles. Kir6.2-containing KATP channels in brain also are involved in protection from hypoxia-induced generalized seizure. In cardiovascular tissues, Kir6.1-containing KATP channels are involved in regulation of vascular tonus. In addition, the Kir6.1 null mouse is a model of Prinzmetal angina in humans. Our studies of Kir6.2 null and Kir6.1 null mice reveal that KATP channels are critical metabolic sensors in acute metabolic changes, including hyperglycemia, hypoglycemia, ischemia, and hypoxia.
Diabetes 2004 Dec
PMID:Roles of ATP-sensitive K+ channels as metabolic sensors: studies of Kir6.x null mice. 1556 8

Coronary artheroclerosis in diabetes patients can be divided into 2 phases, one is seen in the early phase of diabetes or insulin resistance syndrome as unstable plaque with lipid-rich core, thinner fibrous caps and small dose or a lack of calcification and the other in the late or advanced stage of diabetes is hard and stable plaque with much fibrous protein and calcification which extends from truncal to peripheral areas. In diabetic patients in the late stage, coronary accidents occur as the chronic multiple vessel diseases with a lot of calcification, while in the early stage of diabetes vasospastic angina and acute coronary syndrome with less calcification tends to occur. We can find out the coronary calcification by EBCT or 3DCT easily which is characteristic in patients of diabetes complicated with coronary artery disease and in the early stage the stenosis of left truncal artery or large vessels of LAD can be detectable by 3DCT.
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PMID:[Assessment of coronary calcification by computed tomography inclusive of 3DCT]. 1577 96

We investigated to what extent patients with variant angina and significant coronary stenosis (>or=70%) present a clinical and angiographic profile similar to patients with ST elevation myocardial infarction. Thus, the clinical and angiographic features as well as follow-up events of 200 patients were prospectively analyzed and were compared with those of 422 patients with a first ST elevation myocardial infarction survivors of the early phase (3 days) and those of 70 patients with variant angina and non significant stenosis. Age and incidence of smoking, systemic hypertension, diabetes and maximum ST elevation were similar in the 2 groups. Furthermore, among patients with significant coronary stenosis, stenosis severity and the proportion of eccentric lesions were also comparable. Incidence of recent-within 30 days prior to admission-angina at rest was higher in variant angina patients with significant stenosis (67% vs. 27%, p<0.001) than in those with myocardial infarction but long standing angina at rest (>30 days) was low and comparable in these 2 groups (15% vs. 11%, ns). Also, in a 5-year follow-up most patients from these 2 groups were free from angina at rest (86% vs. 84%) which in variant angina patients was largely attributable to a high revascularization rate (72%). Moreover, the rate of myocardial infarction/cardiac death (20% vs. 19%) was also similar. Patients with variant angina and non-significant stenosis, however, had longer antecedent angina, more frequent follow-up angina and a lower incidence of cardiac events than the other 2 groups. Thus, these findings suggest that patients with variant angina and significant coronary stenosis generally behave as an acute coronary syndrome-likely associated with an acutely complicated plaque-rather than as recurrent vasospastic angina, and should be managed accordingly.
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PMID:Comparison of clinical and angiographic features and longterm follow-up events between patients with variant angina and patients with ST elevation myocardial infarction. 1630 10


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