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)

In a prospective multicentre study described previously on prediabetic events in siblings of index cases with insulin-dependent diabetes mellitus, 31 children developed clinical diabetes during the observation period and 51 children seroconverted for islet cell antibodies or insulin autoantibodies. By using nonserotype specific EIA and RIA, it has shown recently that enterovirus infections in both groups were frequently associated with increases of islet cell antibody and/or insulin autoantibody titres. Serum specimens sequentially collected from 12 children during the prediabetic period were still available and were then tested for serotype-specific neutralizing antibodies. Plaque-neutralization assays were carried out for coxsackievirus A9, coxsackievirus B types 1 to 6, and echovirus types 1 and 11. An unequivocal monotypic increase in neutralizing antibodies was observed on seven occasions in six children, on one occasion with coxsackievirus A9, one with coxsackievirus B1, two with coxsackievirus B2, two with coxsackievirus B3, and one with coxsackievirus B5. In four patients, the infection was associated temporally with increases in the levels of islet cell antibodies, insulin autoantibodies and/or antibodies to glutamic acid decarboxylase, and in three other patients, it coincided with the clinical onset of insulin-dependent diabetes mellitus. These results suggest that the association of enterovirus infections with insulin-dependent diabetes mellitus is not restricted to serotype 4 of coxsackie B viruses suspected previously, but that several different serotypes might play a role in the pathogenesis of the disease.
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PMID:Several different enterovirus serotypes can be associated with prediabetic autoimmune episodes and onset of overt IDDM. Childhood Diabetes in Finland (DiMe) Study Group. 970 Jun 36

Acute coronary syndromes (ACS) such as unstable angina, myocardial infarction, or sudden ischemic death evolve from coronary thrombosis consequence of atherosclerotic plaque disruption. Plaque stabilization is an important therapeutic strategy in the prevention of ACS. Coronary risk factors include age, male sex, cigarette smoking, hypertension, dislipidemia, diabetes mellitus, insulin resistance and/or hyper insulinemia, obesity, sedentary lifestyle, stress, and the morning surge of sympathetic activity. New risk factors are emerging such as high homocystein, inflammation, and some kinds of infection. Control of blood pressure and cholesterol clearly reduce the risk of coronary events and mortality although the effects of antihypertensive therapy have been less than expected. The benefits of smoking cessation, moderate alcohol consumption, low-dose aspirin prophylaxis, estrogen-replacement therapy in postmenoposal women have also been shown.
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PMID:[Risk factors and prevention of acute coronary syndrome]. 979 37

The diagnosis coronary artery disease is classically based on patient's symptoms and morphology, as analyzed by angiography. The importance of risk factors for the development of coronary atherosclerosis and disturbance of coronary vasomotion is clearly established. However, microembolization of the coronary circulation has also to be taken into account. Microembolization may occur as a single or as multiple, repetitive events, and it may induce inflammatory responses. Spontaneous microembolization may occur, when the fibrous cap of an atheroma or fibroatheroma (Stary i.v. and Va) ruptures and the lipid pool with or without additional thrombus formation is washed out of the atheroma into the microcirculation. Such events with progressive thrombus formation are known as cyclic flow variations. Plaque rupture occurs more frequently than previously assumed, i.e. in 9% of patients without known heart disease suffering a traffic accident and in 22% of patients with hypertension and diabetes. Also, in patients dying from sudden death microembolization is frequently found. Patients with stable and unstable angina show not only signs of coronary plaque rupture and thrombus formation, but also microemboli and microinfarcts, the only difference between those with stable and unstable angina being the number of events. Appreciation of microembolization may help to better understand the pathogenesis of ischemic cardiomyopathy, diabetic cardiomyopathy and acute coronary syndromes, in particular in patients with normal coronary angiograms, but plaque rupture detected by intravascular ultrasound. Also, the benefit from glycoprotein IIb/IIIa receptor antagonist is better understood, when not only the prevention of thrombus formation in the epicardial atherosclerotic plaque, but also that of microemboli is taken into account. Microembolization also occurs during PTCA, inducing elevations of troponin T and I and elevations of the ST segment in the EKG. Elevated baseline coronary blood flow velocity, as a potential consequence of reactive hyperemia in myocardium surrounding areas of microembolization, is more frequent in patients with high frequency rotablation than in patients with stenting and in patients with PTCA. The hypothesis of iafrogenic microembolization during coronary interventions is now supported by the use of aspiration and filtration devices, where particles with a size of up to 700 microns have been retrieved. In the experiment, microembolization is characterized by perfusion-contraction mismatch, as the proportionate reduction of flow and function seen with an epicardial stenosis is lost and replaced by contractile dysfunction in the absence of reduced flow. The analysis of the coronary microcirculation, in addition to that of the morphology and function of epicardial coronary arteries, and in particular appreciation of the concept of microembolization will further improve the understanding of the pathophysiology and clinical symptoms of coronary artery disease.
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PMID:Coronary microembolization--its role in acute coronary syndromes and interventions. 1060 63

The purpose of this study was to investigate the histological characteristics of atheromatous carotid plaque, and to analyze the relationship between the angiographic findings and the clinical features. We retrospectively reviewed 55 cases of carotid endarterectomy for extracranial internal carotid artery stenosis, who were treated at our institute from January 1995 to December 1997. The histological examination included hematoxylin-eosin staining, Masson-trichrome staining, and immunostaining for antismooth muscle antibody and anti-CD68 antibody. The main compositions of the carotid plaque included synthetic type vascular smooth muscle cells and extracellular matrix. The histological findings showed ulceration in 49 (89.1%) cases, calcium deposits in 42 (76.4%) cases, and an inflammatory reaction in 44 (80.0%) cases. Neurological abnormalities were strongly associated with plaque ulceration (P = 0.045) and an inflammatory reaction (P = 0.013), whereas no correlation existed regarding calcium deposits (P = 0.173). The angiographic findings showed ulceration in 46 (83.6%) cases. Plaque ulceration in the angiography findings showed no statistically significant correlation with the histologic findings (P = 0.410) and preoperative neurologic abnormalities (P = 0.059). All of the atherosclerotic risk factors such as hypertension, smoking, diabetes mellitus, hyperlipidemia, and myocardial infarction had no statistically significant correlation with the histological features of the carotid plaque. In conclusion, the main compositions of carotid plaque were synthetic-type vascular smooth muscle cells and extracellular matrix. The histological ulceration and inflammatory reaction of the plaque showed a statistically significant correlation with the preoperative neurologic symptoms, whereas no correlation was seen in the calcium deposits. Angiographic ulceration showed no correlation with the histological findings or preoperative neurologic abnormalities. In addition, the histological findings showed no correlation with the atherosclerotic risk factors.
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PMID:The relationship between the angiographic findings and the clinical features of carotid artery plaque. 1064 81

Hemodialysis patients frequently show associated hypertension, which can lead to a number of cardiovascular complications. The aim of this study was to assess the effects of hypertension on the structure and function of the carotid artery and left ventricle (LV) in hemodialysis patients. In addition, we investigated the contribution of hemodialysis and other risk factors. Fifty-two hemodialysis patients, 71 hypertensive patients (HT group) and 30 normotensive subjects (NT group) were included in this study. Hemodialysis patients were divided into two groups: 35 patients with hypertension (HDHT group), and 17 patients without hypertension (HDNT group). We measured intima-media thickness (IMT), plaque score, end-diastolic diameter, and stiffness index beta of the carotid artery by ultrasonography, and LV mass index (LVMi), endocardial fractional shortening (FS), and midwall FS (MWS) by echocardiography. A multiple stepwise regression analysis including hemodialysis, hypertension, diabetes mellitus, and other risk factors was also performed. IMT was significantly higher in the HT and HDHT groups than in the NT group. Plaque score and diameter of the carotid artery were higher in the HDHT group than in the other three groups. The stiffness index beta was higher in the HDHT group than in the non-hemodialysis groups. In multivariate analysis, IMT was independently correlated with age and hypertension. Plaque score and stiffness index beta were independently associated with age, hypertension, and hemodialysis. LVMi was higher in HT and hemodialysis-patients groups than in the NT group. Hypertension and hemodialysis were strong and independent predictors of LVMi. FS showed no significant differences among the four groups, but MWS was significantly lower among the hemodialysis patients than in the NT group. MWS was independently correlated with hemodialysis and diabetes. In conclusion, hemodialysis per se advanced both atherosclerosis and arteriosclerosis of the carotid artery. Moreover, it increased LVMi and caused cardiac dysfunction. Associated hypertension might thus accelerate the progression of atherosclerosis and arteriosclerosis of the carotid artery and the increase of LVMi.
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PMID:Structure and function of the left ventricle and carotid artery in hemodialysis patients. 1140 44

Insulin resistance is a characteristic feature of type II diabetes as well as obesity. This insulin resistant state at the peripheral tissue level causes impaired glucose utilization, leading to hyperglycemia. Studies of antidiabetic agents by Takeda originated more than three decades ago when KK mice were introduced, followed by the development of a highly insulin-resistant animal model, KKAy mice. The first 2,4-thiazolidinedione derivative AL-321, which exhibited hypoglycemic effects in KKAy mice, was discovered by modification of the hypolipidemic agent AL-294 as a lead compound. Extensive structure-activity relationship studies on the analogues of AL-321 led to the selection of ciglitazone (ADD-3878) as a candidate for clinical evaluation. Ciglitazone, a prototypical compound in the series, was shown to normalize hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in various insulin-resistant animal models without altering normoglycemia in nondiabetic animal models. However, it appeared that a more potent compound was needed for further clinical evaluation of this class of compound. Further study of this series of compounds led to the finding of pioglitazone (AD-4833) as a promising clinical candidate. Pioglitazone clearly ameliorates the abnormal glucose and lipid metabolism in diabetic patients and was marketed in the USA in August 1999 for the treatment of type II diabetes. Pioglitazone is now marketed in more than 40 countries world wide. Historical aspects of our studies on pioglitazone and its biological activities are described.
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PMID:[Discovery and development of a new insulin sensitizing agent, pioglitazone]. 1244 Jan 49

Constrictive remodeling occurs in significant atherosclerotic lesions of the diabetic patient, but the impact of diabetes mellitus (DM) on the angiographically normal coronary artery is still unclear. Morphometric analysis using intravascular ultrasound (IVUS) prior to intervention evaluated 54 sites in 33 DM patients and 106 in 62 non-diabetic patients. Vessel area (VA) and lumen area (LA) were measured at angiographically normal sites in the vessel. Plaque area (PA) was calculated as VA - LA. Percentage plaque area (%PA) was calculated as PA VA. Even in the angiographically normal site, mild coronary atherosclerosis was detected by IVUS in both groups. In the patients with DM, VA and LA were significantly smaller than in the non-diabetic patient (15.5 vs 17.8 mm(2), p<0.01; and 10.1 vs 12.2 mm(2), p<0.01 respectively), whereas % PA was similar (34.5 vs 31.6%). At angiographically normal sites where mild coronary atherosclerosis is detected by IVUS, the coronary artery of diabetic patients is smaller than that of the non-diabetic. These results suggest impaired compensatory enlargement or some other constrictive mechanism has already occurred in the early stages of coronary atherosclerosis in patients with DM.
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PMID:Impact of diabetes mellitus on angiographically silent coronary atherosclerosis. 1273 81

The objective of this study was to elucidate the association between the polymorphism of stromelysin-1, also called matrix metalloproteinases-3 (MMP-3), and smoking in the pathogenesis of young acute myocardial infarction (MI). Plaque rupture is well established as a critical factor in the pathogenesis of acute MI. MMP-3 can degrade extracellular matrix and are identified extensively in human coronary atheroslcerotic plaques, and may contribute to the weakening of the cap and subsequent rupture. We studied 150 consecutive patients with acute MI onset at age under 45 years (84% men) and 150 sex- and age-matched control subjects. 5A/6A genotype in the stromelysin-1 promoter was determined using polymerase chain reaction and direct sequencing. Results show that the frequency of the 5A allele and the prevalence of 5A/5A + 5A/6A genotypes were both significantly higher in the young MI than the control group (35.0% vs. 20.0%, odds ratio [OR] 2.15, 95% confidence interval [CI] 1.30 to 6.80, p<0.001; 44.7% vs. 27.4%, OR 2.19, 95% CI 1.21 to 3.98, p=0.009). Multiple logistic regression analysis showed that the 5A allele was an independent risk factor (OR 2.36, 95% CI 1.24 to 5.90, p=0.008) as were as smoking (OR 3.92, 95% CI 1.75 to 9.21, p=0.001), diabetes mellitus (OR 3.51, 95% CI 1.41 to 6.32, p=0.0068) and hypertension (OR 1.85, 95% CI 1.35 to 4.33, p=0.0025) for the premature onset of MI. Compared to 6A/6A subjects, among patients who did not smoke, the 5A allele polymorphism was associated with a higher risk of MI at a young age (OR 2.69, 95% CI 1.3 to 8.6), but smoking carriers of the 5A allele had a significantly 10-fold higher risk of MI (OR 9.98, 95% CI 2.3 to 12.5). We can conclude that there was a significant association between the 5A/6A polymorphism in the promoter region of stromelysin-1 gene and young MI in Taiwan. A synergistic effect between smoking and this polymorphism for the premature onset of MI had been shown in this study.
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PMID:Synergistic effect of stromelysin-1 (matrix metallo-proteinase-3) promoter 5A/6A polymorphism with smoking on the onset of young acute myocardial infarction. 1287 19

The periodontal condition of 72 non-insulin dependent diabetes patients was compared with that of 92 nondiabetic individuals. Plaque Index (PII), Calculus Index (CI), Gingival Index (GI), and attachment loss (AL) were measured on four surfaces of six teeth in each subject. All four parameters were significantly higher in the diabetic group. No significant difference in the frequency of toothbrushing was found between the groups. For all age groups, GI and AL were higher in the diabetic group. In each group, GI was not changed with age, while AL increased with age. Classification of the groups based on PII showed that the diabetic group's GI was higher than the nondiabetic group for low, medium, or high PII values. The diabetic group showed higher AL for only the medium and high PII groups. Classification by CI revealed that the diabetic group's GI and AL were significantly higher than those of the nondiabetic group for subjects with low, medium, or high values of CI. Multiple regression analysis revealed that the main factor affecting GI was the presence or absence of diabetes. PII and CI both showed a significant relationship with GI; age was the second most significant factor. The most significant factors influencing AL were CI and the presence or absence of diabetes; age was the second most significant factor. Patients who had had diabetes for more than 10 years had a higher AL than those who had suffered from diabetes for less than 10 years. Patients with average HbA1c values > or = 10% had more serious mean GI values than those with HbA1c values < 10%. In patients with diabetes, age, plaque accumulation, and calculus formation have more detrimental effects on the periodontal apparatus than in healthy individuals.
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PMID:Cross-sectional analysis of different variables of patients with non-insulin dependent diabetes and their periodontal status. 1498 48

We evaluated the influence of diabetes on plaque volume and vessel size at a reference segment in diabetic patients undergoing percutaneous coronary intervention using both angiograms and quantitative intravascular ultrasound. A total of 344 patients with 449 de novo coronary lesions including 97 diabetics (133 lesions) who underwent elective percutaneous coronary intervention under intravascular ultrasound guidance were included in this study. Eleven diabetic patients (19 lesions) received insulin and 52 patients (77 lesions) oral hypoglycemic drugs. The other 34 patients (37 lesions) received diet/exercise therapy alone. We measured vessel area (VA) and lumen area (LA) at proximal and distal reference segments by intravascular ultrasound, which were averaged. Plaque area (VA-LA) and % plaque area (100 x plaque area/VA) were subsequently calculated. Although VA was similar between diabetic and non-diabetic patients (13.46 +/- 4.49 mm2 in diabetics versus 14.11 +/- 5.24 mm2 in non-diabetics, P = 0.214), LA was smaller (6.51 +/- 2.63 mm2 versus 7.38 +/- 3.08 mm2, P = 0.004) and % PA was larger (50.4 +/- 11.7 versus 46.5 +/- 11.3, P < 0.001) in diabetic patients, especially the group receiving a hypoglycemic drug or insulin. VA, LA, and % PA were similar between patients with and without insulin treatment. These results potentially might cause undersized device selection without intravascular ultrasound guidance.
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PMID:The influence of diabetes mellitus on plaque volume and vessel size in patients undergoing percutaneous coronary intervention. 1535 68


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