cardiovascular-agents and Diabetes-Mellitus--Type-1

Chemokines are critical components in pathology. The roles of chemokine CC motif ligand 4 (CCL4) and its receptor are associated with diabetes mellitus (DM) and atherosclerosis cardiovascular diseases. However, due to the complexity of these diseases, the specific effects of CCL4 remain unclear, although recent reports have suggested that multiple pathways are related to CCL4. In this review, we provide an overview of the role and potential mechanisms of CCL4 and one of its major receptors, fifth CC chemokine receptor (CCR5), in DM and cardiovascular diseases. CCL4-related mechanisms, including CCL4 and CCR5, might provide potential therapeutic targets in DM and/or atherosclerosis cardiovascular diseases.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Chemokine CCL4; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Ligands; Receptors, CCR5; Signal Transduction

Our aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF).. We pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF. Stroke occurred in 165 patients (4.7%) with AF and in 206 patients (3.4%) without AF (rates 16.8/1000 patient-years and 11.1/1000 patient-years, respectively). Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74). N-terminal pro B-type natriuretic peptide (available in 2632 patients) was also an independent predictor of stroke (hazard ratio, 1.31; 1.11-1.57 per log unit) when added to this model. With the use of a risk score formulated from these predictors, we found that patients in the upper third of risk had a rate of stroke that approximated the risk in patients with AF.. A small number of demographic and clinical variables identified a subset of patients who have heart failure without AF at a high risk of stroke.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Benzimidazoles; Biomarkers; Biphenyl Compounds; Cardiovascular Agents; Diabetes Mellitus, Type 1; Fatty Acids, Omega-3; Female; Fluorobenzenes; Follow-Up Studies; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Pyrimidines; Randomized Controlled Trials as Topic; Risk Factors; Rosuvastatin Calcium; Stroke; Stroke Volume; Sulfonamides; Tetrazoles

In November 2009 the first European guidelines were presented regarding preoperative risk assessment and perioperative management in non-cardiac surgery. They were designed by the European Society of Cardiology (ESC) and endorsed by the European Society of Anesthesiology.In a standardized manner, patient-specific clinical variables, their exercise capacity and surgery-specific risk factors are summarized to a recommendation concerning medication and preoperative cardiac evaluation. These guidelines are straightforward and feasible for cardiologists as well as specialists in internal medicine and general practicioners. Nevertheless, some points still lack evidence.

Topics: Activities of Daily Living; Age Factors; Angina Pectoris; Cardiovascular Agents; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Angiography; Diabetes Mellitus, Type 1; Electrocardiography; Europe; Evidence-Based Medicine; Exercise Test; Health Status Indicators; Heart Failure; Humans; Metabolic Equivalent; Practice Guidelines as Topic; Preoperative Care; Renal Insufficiency

We assessed the outcomes in diabetic patients undergoing percutaneous coronary intervention (PCI) using sirolimus-eluting stents (SES) as a function of treatment with glycoprotein (GP) IIb/IIIa inhibitors.. Of 551 diabetic patients treated with a SES in nine trials (RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS, REALITY, SVELTE, DIRECT, SIRIUS 2.25, and SIRIUS 4.0), 187 patients (33.9%) were administered GP IIb/IIIa inhibitors during PCI. GP IIb/IIIa blockade was associated with lower rates of myocardial infarction (MI) at 30 days (1.1% vs. 3.3%, P = 0.12) and at 1 year (1.1% vs. 4.7%, P = 0.04), and composite endpoint of cardiac death/MI at 1 year (2.2% vs. 6.2%, P = 0.05). Benefit from GP IIb/IIIa inhibitors was confined to 128 insulin-treated diabetics who had remarkable reduction in MI (0.0% vs. 6.3%, P = 0.04) and cardiac death/MI at 30 days (0.0% vs. 7.6%, P = 0.05) and at 1-year (0.0% vs. 13.4%, P = 0.01 and 0.0% vs. 15.7%, P = 0.0005, respectively). When treated with GP IIb/IIIa inhibitors, insulin-requiring diabetics had similar rates of 1-year death/MI when compared with the nondiabetic patients (0% vs. 4.7%, P = 0.13, respectively). There were no significant differences in outcomes as a function of GP IIb/IIIa blockade in diabetics not treated with insulin.. In this analysis, outcomes of insulin requiring diabetic patients undergoing PCI with SES were considerably improved with adjunctive GP IIb/IIIa inhibitors by decreasing the rates of MI and composite endpoint of cardiac death/MI.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 1; Drug-Eluting Stents; Female; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Proportional Hazards Models; Risk Assessment; Sirolimus; Time Factors; Treatment Outcome

Diabetes mellitus is a major risk factor for restenosis in patients undergoing percutaneous coronary intervention. Randomized controlled trials comparing drug-eluting stents (DESs) with bare metal stents (BMSs) showed a marked decrease in in-stent restenosis and target lesion revascularization with DESs in the total patient population enrolled in the studies, including patients with diabetes. However, it remains unclear whether the antirestenotic benefit of DESs is preserved in the high-risk diabetic subgroup. MEDLINE, EMBASE, ISI Web of Knowledge, Current Contents, International Pharmaceutical Abstracts, and recent Scientific Sessions databases were searched to identify relevant clinical trials comparing DESs with BMSs. A randomized controlled trial was included if it provided outcome data for patients with diabetes for > or =1 of the following: late lumen loss, in-stent restenosis, or target lesion revascularization. Data were combined using fixed-effects models, and standard tests for heterogeneity were performed. Eight studies with 1,520 patients with diabetes were identified that reported > or =1 outcome of interest. Mean late lumen losses (7 studies) were 0.93 mm (95% confidence interval [CI] 0.510 to 1.348) with BMSs and 0.18 mm (95% CI -0.088 to +0.446) with DESs. For patients receiving a DES, this translated into a marked decrease in in-stent restenosis (7 studies, RR 0.14, 95% CI 0.10 to 0.22, p <0.001) and target lesion revascularization (8 studies, RR 0.34, 95% CI 0.26 to 0.45, p <0.001). DES use is associated with a marked decrease in in-stent restenosis and target lesion revascularization in patients with diabetes. In conclusion, the analysis supports the current widespread use of DESs in these high-risk patients.

Topics: Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Databases, Factual; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Follow-Up Studies; Humans; Paclitaxel; Prosthesis Design; Randomized Controlled Trials as Topic; Sirolimus; Stents; Treatment Outcome

Diabetes mellitus is a risk factor for coronarosclerosis and for high mortality after myocardial infarction (MI). The causes of this high mortality are: more extensive and premature coronarosclerosis, more frequent left ventricular dysfunction, worse glycemic control with increased myocardial oxygen consumption, sulfanylurea drugs before and during MI. The results of a multicenter study (DIGAMI) and other studies suggest that a better control of diabetes using intravenous infusion of insulin and glucose, followed by long-term (3 months) intensive insulin therapy subcutaneously, improves long-term prognosis after MI. The relative reduction of mortality at the end of follow-up (3.4 years) is 28%. Thrombolysis reduces mainly mortality in hospital,s period and does not provoke retinal haemorrhages. Aspirin lowers the relative risk of mortality to 0.72. The beta-blockers are less used in diabetic patients because they probably alter diabetic control, lipid profile and "mask" the hypoglycemic symptoms, but the results of the beta-blocker's effect concerning reduction of mortality are convincing. ACE inhibitors and statins also reduce mortality in diabetics with MI, via beneficial influence of endothelial dysfunction. The ATMA study registers reduction of rhythmogenic mortality by 29% with amiodarone in high risk of arrhythmia after MI. The invasive methods of treatment in diabetes are accompanied by higher risk of reobstruction. The attempt to reduce this tendency is realizable with intracoronary stents, glycoprotein IIb/IIIa inhibitors and aggressive early treatment of all other risk factors.

Topics: Cardiovascular Agents; Clinical Trials as Topic; Coronary Artery Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Myocardial Infarction; Risk Factors

Topics: Cardiovascular Agents; Clinical Trials as Topic; Coronary Disease; Diabetes Mellitus, Type 1; Female; Humans; Male; Myocardial Infarction; Prognosis

The DIABETES (DIABETes and sirolimus-Eluting Stent) trial is a prospective, multicentre, randomised, controlled trial aimed at demonstrating the efficacy of sirolimus-eluting stent (SES) as compared to bare metal stent (BMS) implantation in diabetic patients. The aim of the present analysis was to assess the five-year clinical follow-up of the patients included in this trial.. One hundred and sixty patients (222 lesions) were included: 80 patients were randomised to SES and 80 patients to BMS. Patients were eligible for the study if they were identified as non-insulin-dependent diabetics (NIDDM) or insulin-dependent diabetics (IDDM), with significant native coronary stenoses in ≥1 vessel. There was a sub-randomisation according to diabetes status. Clinical follow-up was extended up to five years. Five-year clinical follow-up was obtained in 96.2%. Overall, MACE at five years was significantly lower in the SES group as compared with the BMS arm, mainly due to a significant reduction in TLR. There were no significant differences in cardiac death or myocardial infarction (MI). This was also observed in both prespecified subgroups IDDM and NIDDM. In the SES group, the incidence density of definite/probable stent thrombosis was 0.53 per 100 person-years, whereas in the BMS group it was 0.8 per 100 person-years. Independent predictors of MACE were: SES implantation (p<0.001), multivessel stent implantation (p=0.04), and creatinine levels (p=0.001).. Five-year follow-up of the DIABETES trial suggests the effect of SES in reducing TLR is similar in both IDDM and NIDDM. No major safety concerns in terms of ST, MI or mortality were observed.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Stenosis; Coronary Thrombosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Drug-Eluting Stents; Female; Humans; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Risk Factors; Severity of Illness Index; Sirolimus; Spain; Stents; Time Factors; Treatment Outcome

The aims of the present study were, firstly, to evaluate long-term trends in the occurrence and treatment of cardiovascular disease (CVD) risk factors and the occurrence of CVD events in children with type 1 diabetes mellitus (T1DM) and, secondly, to assess the determinants of undertreatment of CVD risk factors.. A retrospective cohort study was conducted in 3728 children (<19 years of age) with T1DM and up to 5 age- and gender-matched diabetes-free children (reference cohort) (n = 18 513) using data from the Clinical Practice Research Datalink (CPRD).. Compared with diabetes-free subjects, children with T1DM had significantly higher annual prevalence rates of CVD risk factors and cardiovascular (CV) medication use 20 years after the onset of diabetes (index date): hypertension: 35.2% vs. 11.4%, P < 0.001; hypercholesterolaemia: 66.7% vs. 7.14%, P < 0.001; and CV medication use: 37.0% vs. 3.6%, P < 0.001. The significant differences between prevalence rates in the two cohorts started from 1 year before the index date. Furthermore, 50% of the children in the T1DM cohort with hypertension and 53% with hypercholesterolaemia remained untreated with CV drugs for a period of 2-5 years during the 20-year follow-up. Age was the only determinant associated with undertreated hypertension in the T1DM cohort.. Children with T1DM had substantially higher prevalence rates of hypertension and hypercholesterolaemia from 1 year before up to 20 years after the onset of diabetes compared with nondiabetics. There is a substantial undertreatment of CVD risk factors with CV drugs. In children with T1DM, screening for CVD risk factors and adequate treatment are of the utmost importance to prevent CVD later in life.

Topics: Adolescent; Age Factors; Cardiovascular Agents; Cardiovascular Diseases; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Humans; Hypercholesterolemia; Hypertension; Infant; Male; Prevalence; Retrospective Studies; Risk Factors; Young Adult

Recent clinical trials of new glucose-lowering treatments have drawn attention to the importance of hospitalization for heart failure as a complication of diabetes mellitus. However, the epidemiology is not well described, particularly for type 1 diabetes mellitus. We examined the incidence and case-fatality of heart failure hospitalizations in the entire population aged ≥30 years resident in Scotland during 2004 to 2013.. Date and type of diabetes mellitus diagnosis were linked to heart failure hospitalizations and deaths using the national Scottish registers. Incidence rates and case-fatality were estimated in regression models (quasi-Poisson and logistic regression respectively). All estimates are adjusted for age, sex, socioeconomic status, and calendar-year.. Over the 10-year period of the study, among 3.25 million people there were 91, 429, 22 959, and 1313 incident heart failure events among those without diabetes mellitus, with type 2, and type 1 diabetes mellitus, respectively. The crude incidence rates of heart failure hospitalization were therefore 2.4, 12.4, and 5.6 per 1000 person-years for these 3 groups. Heart failure hospitalization incidence was higher in people with diabetes mellitus, regardless of type, than in people without. Relative differences were smallest for older men, in whom the difference was nonetheless large (men aged 80, rate ratio 1.78; 95% CI, 1.45-2.19). Rates declined similarly, by 0.2% per calendar-year, in people with type 2 diabetes mellitus and without diabetes mellitus. Rates fell faster, however, in those with type 1 diabetes mellitus (2.2% per calendar-year, rate ratio for type 1/calendar-year interaction 0.978; 95% CI, 0.959-0.998). Thirty-day case-fatality was similar among people with type 2 diabetes mellitus and without diabetes mellitus, but was higher in type 1 diabetes mellitus for men (odds ratio, 0.96; 95% CI, 0.95-0.96) and women (odds ratio, 0.98; 95% CI, 0.97-0.98). Case-fatality declined over time for all groups (3.3% per calendar-year, odds ratio per calendar-year 0.967; 95% CI, 0.961-0.973).. Despite falling incidence, particularly in type 1 diabetes mellitus, heart failure remains ≈2-fold higher than in people without diabetes mellitus, with higher case-fatality in those with type 1 diabetes mellitus. These findings support the view that heart failure is an under-recognized and important complication in diabetes mellitus, particularly for type 1 disease.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Heart Failure; Hospitalization; Humans; Incidence; Logistic Models; Male; Middle Aged; Odds Ratio; Risk Factors; Survival Analysis; Young Adult

Topics: Animals; Arterioles; Benzimidazoles; Cardiovascular Agents; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Enzyme Inhibitors; Hypoglycemic Agents; Indoles; Islets of Langerhans Transplantation; Male; Maleimides; Neurotransmitter Agents; Neurovascular Coupling; Pia Mater; Potassium Chloride; Protein Kinase C; Rats, Inbred Lew; Receptors, KIR; Sciatic Nerve

To investigate the 5-yr prevalence and incidence rates of cardiovascular medication and cardiovascular disease before and after onset of type 1 diabetes (T1D) in children and adolescents.. Children and adolescents (<19 yr) with T1D (n = 925), defined as those who received at least two insulin prescriptions, and a four times larger reference cohort (n = 3591) with the same age and gender in the Dutch PHARMO Record Linkage System (RLS) were studied in a retrospective cohort study between 1999 and 2009. The date of first insulin dispensing was selected as the index date.. The overall prevalence rate of cardiovascular medication use was substantially higher in the T1D cohort before (2.2 vs. 1.0%, p < 0.001) and after (9.2 vs. 3.2%, p < 0.001) the index date. After the index date angiotensin-converting enzyme inhibitors (2.0%) and statins (1.5%) were the most prevalent cardiovascular medications in the T1D cohort. The highest incidence rate of cardiovascular medication use was observed in the first year after the index date [28.1 per 1000 person years (PY)]. Furthermore, three type 1 diabetic patients were hospitalized due to cardiomyopathy (n = 2) and heart failure (n = 1) and one child from the reference group was hospitalized due to cardiomyopathy in the 5 yr after the index date.. Children with T1D were more likely to use cardiovascular medications in the years before and after the onset of diabetes. Our study emphasizes the importance of routine screening tests and timely treatment of CVD risk factors in the pediatric population with diabetes.

Topics: Adolescent; Cardiovascular Agents; Cardiovascular Diseases; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Humans; Incidence; Infant; Male; Netherlands; Prevalence; Retrospective Studies

This study sought to compare everolimus-eluting stents (EES) versus Resolute zotarolimus-eluting stents (ZES) in terms of patient- or stent-related clinical outcomes in an "all-comer" group of patients with diabetes mellitus (DM) who underwent percutaneous coronary intervention.. DM significantly increases the risk of adverse events after percutaneous coronary intervention. The efficacy and safety of second-generation drug-eluting stents, in particular EES versus ZES, in patients with DM have not been extensively evaluated.. Patients with DM (1,855 of 5,054 patients, 36.7%) from 2 prospective registries (the EXCELLENT [Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting] registry and RESOLUTE-Korea [Registry to Evaluate the Efficacy of Zotarolimus-Eluting Stent]) who were treated with EES (n = 1,149) or ZES (n = 706) were compared. Stent-related outcome was target lesion failure (TLF), and patient-oriented composite events were a composite of all-cause mortality, any myocardial infarction, and any revascularization.. Despite a higher risk patient profile in the ZES group, both TLF (43 of 1,149 [3.7%] vs. 25 of 706 [3.5%], p = 0.899) and patient-oriented composite events (104 of 1,149 [9.1%] vs. 72 of 706 [10.2%], p = 0.416) were similar between the EES and ZES in patients with DM at 1 year. In those without DM, EES and ZES also showed comparable incidence of TLF (39 of 1,882 [2.1%] vs. 33 of 1,292 [2.6%], p = 0.370) and patient-oriented composite events (119 of 1,882 [6.3%] vs. 81 of 1,292 [6.3%], p = 0.951), which were all significantly lower than in the DM patients. These results were corroborated by similar findings from the propensity score-matched cohort. Upon multivariate analysis, chronic renal failure was the most powerful predictor of TLF in DM patients (hazard ratio: 4.39, 95% confidence interval: 1.91 to 10.09, p < 0.001).. After unrestricted use of second-generation drug-eluting stents in all-comers receiving percutaneous coronary intervention, both EES and ZES showed comparable clinical outcomes in the patients with DM up to 1 year of follow-up. DM compared with non-DM patients showed significantly worse patient- and stent-related outcomes. Nonetheless, overall incidences of TLF were low, even in the patients with DM, suggesting excellent safety and efficacy of both types of second-generation drug-eluting stents in this high-risk subgroup of patients.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Patient Selection; Percutaneous Coronary Intervention; Propensity Score; Proportional Hazards Models; Prosthesis Design; Registries; Republic of Korea; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Topics: Absorbable Implants; Cardiovascular Agents; Coronary Artery Disease; Coronary Stenosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Percutaneous Coronary Intervention; Sirolimus

Topics: Cardiovascular Agents; Contraceptive Agents; Contraindications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Humans; Pregnancy

Haemodynamic changes that occur during pregnancy are maximal between 28 and 34 weeks. In the pregnant woman with several associated diseases, such as hypertensive myocardiopathy and pre-gestational diabetes, these changes can lead to a difficult control of pulmonary hypertension and acute pulmonary oedema. We report the case of a pregnant woman with long term type 1 diabetes mellitus who suffered pre-eclampsia in a previous pregnancy, and since then developed hypertensive cardiomyopathy. She was admitted at 30 week gestation for metabolic and blood pressure control, and developed congestive cardiac failure after the administration of betamethasone for foetal lung maturity. A transthoracic echocardiogram showed a non-dilated hypertrophic left ventricle with good systolic function, restrictive diastolic dysfunction and moderate pulmonary arterial hypertension. When her general condition improved, we performed a caesarean section under regional anaesthesia to prevent the complications of pulmonary and systemic hypertension. We present the anaesthetic management and resolution of complications after oxytocin administration.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Betamethasone; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Cesarean Section, Repeat; Diabetes Mellitus, Type 1; Diastole; Female; Heart Failure; Humans; Hypertension, Pulmonary; Hypotension; Infant, Newborn; Intraoperative Complications; Norepinephrine; Oxytocin; Phenylephrine; Pre-Eclampsia; Preanesthetic Medication; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy in Diabetics; Supine Position

To describe contraception use and the prescription of drugs that are either not recommended in pregnancy or are potentially teratogenic by diabetes type in women of child-bearing age.. Retrospective, cross-sectional chart review undertaken in 22 general practices in Warwickshire, UK. Demographic, anthropometric, medical history, medication and contraception data were extracted from women aged 14 to 49 years with pre-existing diabetes. Independent sample t-test, Mann-Whitney test and χ(2) -test were used to test for univariable associations and multiple logistic regression was used to adjust for confounders.. Four hundred and seventy eligible women were identified; the majority had a diagnosis of Type 2 diabetes (67%). Thirty-six per cent and 64% of women with Type 1 and Type 2 diabetes, respectively, were prescribed drugs not recommended for use in pregnancy (P < 0.001). Less than half were using concomitant contraception (P < 0.001). No significant difference of contraception use was observed between women who were and were not taking drugs not recommended for use in pregnancy (40 vs. 41%, P = 0.4).. Use of drugs not recommended during pregnancy in women with diabetes of child-bearing age is common but is not associated with increased use of contraception. There is need to identify and overcome barriers to effective contraception use for this population group in order to facilitate optimal management of cardiovascular risk.

Topics: Adolescent; Adult; Cardiovascular Agents; Contraceptive Agents; Contraindications; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Humans; Middle Aged; Pregnancy; Prescription Drugs; Retrospective Studies; Risk Factors; Teratogens; Young Adult

A 23-year-old male patient, who suffers from beta-thalassemia major, came to us for an endocrine-metabolic evaluation. Medical history showed a diagnosis of heart disease with heart failure since the age of 16, type 1 diabetes mellitus diagnosed at the age of 18, treated with an intensive insulin therapy with a poor glycometabolic control. Patient performed regular blood transfusions and iron chelation with deferasirox. An echocardiogram revealed an enlarged left ventricle. Patient had undergone a comprehensive study of buoyancy both basal and hormone-stimulated and it was therefore carried out a diagnosis of GH deficiency and hypogonadotropic hypogonadism. A recombinant GH replacement therapy was then prescribed. After six months of therapy, the patient reported a net improvement of asthenic symptoms. Physical examination showed a reduction in abdominal adiposity in waist and an increase of 5 cm in stature. Laboratory tests showed an amelioration of glycometabolic control, such as to justify a reduction in daily insulin dose. The stature observed was thought appropriate to begin the administration of testosterone. Moreover, the cardiological framework showed a reduction of left ventricular dilatation, good ventricular motility, global minimum persistent tricuspid but not mitral regurgitation and no alteration on ECG.

Topics: Asthenia; beta-Thalassemia; Blood Transfusion; Cardiovascular Agents; Chelation Therapy; Combined Modality Therapy; Diabetes Mellitus, Type 1; Dwarfism; Growth Hormone; Heart Failure; Human Growth Hormone; Humans; Hypogonadism; Insulin; Iron Chelating Agents; Iron Overload; Male; Mitral Valve Insufficiency; Testosterone; Tricuspid Valve Insufficiency; Young Adult

Diabetes remains a significant risk factor for restenosis/thrombosis following stenting. Although vascular healing responses following drug-eluting stent (DES) treatment have been characterized previously in healthy animals, comparative assessments of different DES in a large animal model with isolated features of diabetes remains limited. We aimed to comparatively assess the vascular response to paclitaxel-eluting (PES) and everolimus-eluting (EES) stents in a porcine coronary model of streptozotocin (STZ)-induced type I diabetes.. Twelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic β-cells. After two months, each animal received one XIENCE V® (EES) and one Taxus Liberte (PES) stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5 M-10-12 M) after 24 hours on carotid endothelial (EC) and smooth muscle (SMC) cell viability under hyperglycemic (42 mM) conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5 M, 10-7 M) for 24 hours.. After 3 months, EES reduced neointimal area (1.60 ± 0.41 mm, p < 0.001) with trends toward reduced % diameter stenosis (11.2 ± 9.8%, p = 0.12) and angiographic late-loss (0.28 ± 0.30 mm, p = 0.058) compared to PES (neointimal area: 2.74 ± 0.58 mm, % diameter stenosis: 19.3 ± 14.7%, late loss: 0.55 ± 0.53 mm). Histopathology revealed increased inflammation scores (0.54 ± 0.21 vs. 0.08 ± 0.05), greater medial necrosis grade (0.52 ± 0.26 vs. 0.0 ± 0.0), and persistently elevated fibrin scores (1.60 ± 0.60 vs. 0.63 ± 0.41) with PES compared to EES (p < 0.05). In vitro, paclitaxel significantly increased (p < 0.05) EC/SMC apoptosis/necrosis at high concentrations (≥ 10-7 M), while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5 M) significantly increased caspase-3 activity (p < 0.05) while everolimus had no effect.. After 3 months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and persistent fibrin compared to EES. Differential effects of everolimus and paclitaxel on vascular cell viability may potentially be a factor in regulating delayed healing observed with PES. Further investigation of molecular mechanisms may aid future development of stent-based therapies in treating coronary artery disease in diabetic patients.

Topics: Animals; Apoptosis; Cardiovascular Agents; Cells, Cultured; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Disease Models, Animal; Dose-Response Relationship, Drug; Drug-Eluting Stents; Endothelial Cells; Everolimus; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Necrosis; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Swine; Time Factors; Wound Healing

Besides alterations in cardiomyocytes themselves, diabetic cardiopathy is characterized by interstitial and microvascular disorders. On the assumption that a specific heart muscle disease develops due to permanently increased oxidative stress on liberation of oxygen-free radicals, adjuvant application of antioxidative therapeutics appears promising in preventing or delaying long-term diabetic complications and protecting the myocardium against acute ischemia. We have investigated the effects of Ginkgo biloba extract (EGb 761), a radical scavenger, against diabetes-induced myocardial interstitium and microvasculature damage, and against additional ischemia/reperfusion injury in spontaneously diabetic BioBreeding/Ottawa Karlsburg (BB/OK) rats modelling diabetic cardiac infarction. Morphological and morphometric parameters in the heart muscle were evaluated by light and electron microscope. We used immunohistochemistry to investigate collagen protein expression as a marker for tissue remodelling together with endothelial nitric oxide synthase (eNOS) protein expression as a marker for endothelial-dependent vasodilation. We also evaluated inflammation response caused by neuropeptide Substance P and interacting mast cells in the diabetic heart. Our results revealed that A) Diabetic myocardium appears more vulnerable to ischemia/reperfusion injury than normal myocardium with regard to myocardial interstitium and microvessel ultrastructure, as well as eNOS protein expression; B) Inflammation response increases in diabetic animals exposed to ischemia/reperfusion injury compared to controls; C) Pre-treatment of diabetic myocardium with EGb results in an improvement of impaired endothelial-dependent vasodilation in diabetes and additional ischemia/ reperfusion, diminished mast cell and substance P accumulation, and better preserved myocardial ultrastructure compared to unprotected myocardium. In conclusion, EGb may act as a potent therapeutic adjuvant in diabetics with respect to ischemic myocardial injury, and may contribute to preventing late complications in diabetic cardiopathy.

Topics: Animals; Cardiovascular Agents; Collagen; Diabetes Complications; Diabetes Mellitus, Type 1; Free Radical Scavengers; Ginkgo biloba; Immunohistochemistry; Male; Microcirculation; Microscopy, Electron, Transmission; Myocardial Reperfusion Injury; Myocardium; Nitric Oxide Synthase Type III; Phytotherapy; Plant Extracts; Rats; Rats, Inbred BB; Substance P

Previous studies reveal major differences in the estimated cardiovascular risk in diabetes mellitus, including uncertainty about the risk in young patients. Therefore, large studies of well-defined populations are needed.. All residents in Denmark > or = 30 years of age were followed up for 5 years (1997 to 2002) by individual-level linkage of nationwide registers. Diabetes patients receiving glucose-lowering medications and nondiabetics with and without a prior myocardial infarction were compared. At baseline, 71 801 (2.2%) had diabetes mellitus and 79 575 (2.4%) had a prior myocardial infarction. Regardless of age, age-adjusted Cox proportional-hazard ratios for cardiovascular death were 2.42 (95% confidence interval [CI], 2.35 to 2.49) in men with diabetes mellitus without a prior myocardial infarction and 2.44 (95% CI, 2.39 to 2.49) in nondiabetic men with a prior myocardial infarction (P=0.60), with nondiabetics without a prior myocardial infarction as the reference. Results for women were 2.45 (95% CI, 2.38 to 2.51) and 2.62 (95% CI, 2.55 to 2.69) (P=0.001), respectively. For the composite of myocardial infarction, stroke, and cardiovascular death, the hazard ratios in men with diabetes only were 2.32 (95% CI, 2.27 to 2.38) and 2.48 (95% CI, 2.43 to 2.54) in those with a prior myocardial infarction only (P=0.001). Results for women were 2.48 (95% CI, 2.43 to 2.54) and 2.71 (95% CI, 2.65 to 2.78) (P=0.001), respectively. Risks were similar for both diabetes types. Analyses with adjustments for comorbidity, socioeconomic status, and prophylactic medical treatment showed similar results, and propensity score-based matched-pair analyses supported these findings.. Patients requiring glucose-lowering therapy who were > or = 30 years of age exhibited a cardiovascular risk comparable to nondiabetics with a prior myocardial infarction, regardless of sex and diabetes type. Therefore, requirement for glucose-lowering therapy should prompt intensive prophylactic treatment for cardiovascular diseases.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Denmark; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Forecasting; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Recurrence; Registries; Risk; Stroke; Survival Analysis

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Mellitus, Type 1; Drug-Eluting Stents; Humans; Hypoglycemic Agents; Insulin; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Research Design; Risk Assessment; Sirolimus; Time Factors; Treatment Outcome

To review the role of cardiovascular disease and therapy in the onset and recurrence of preretinal/vitreous haemorrhage in diabetic patients.. Retrospective case note analysis of diabetic patients with vitreous haemorrhage from the Diabetic Eye Clinic at Birmingham Heartlands Hospital.. In total, 54 patients (mean age 57.1, 37 males, 20 type I vs 34 type II diabetic patients) were included. The mean (SD) duration of diagnosed diabetes at first vitreous haemorrhage was significantly longer, 21.9 (7.6) years for type I and 14.8 (9.3) years for type II diabetic patients (P < 0.01, unpaired t-test, two-tailed).Aspirin administration was not associated with a significantly later onset of vitreous haemorrhage. Four episodes were associated with ACE-inhibitor cough. There was a trend towards HMGCoA reductase inhibitor (statin) use being associated with a delayed onset of vitreous haemorrhage: 21.4 years until vitreous haemorrhage (treatment group) vs 16.2 years (nontreatment group) (P = 0.09, two-tailed, unpaired t-test, not statistically significant). During follow-up 56 recurrences occurred, making a total of 110 episodes of vitreous haemorrhage in 79 eyes of 54 patients. The mean (range) follow-up post haemorrhage was 1067 (77-3842) days, with an average of 1.02 recurrences. Age, gender, diabetes type (I or II) or control, presence of hypertension or hypercholesterolaemia, and macrovascular complications were not associated with a significant effect on the 1-year recurrence rate. Aspirin (and other antiplatelet or anticoagulant agents) and ACE- inhibitors appeared to neither increase nor decrease the 1-year recurrence rate. However, statin use was significantly associated with a reduction in recurrence (Fisher exact P < 0.05; two-tailed) with an odds ratio (95% CI) of 0.25 (0.1-0.95).. In this retrospective analysis, the onset of preretinal/vitreous haemorrhage was not found to be accelerated by gender, hypertension, hypercholesterolaemia, evidence of macrovascular disease, or HbA1c. Neither aspirin nor ACE-inhibitor administration accelerated the onset or recurrence of first vitreous haemorrhage. Statins may have a protective role, both delaying and reducing the recurrence of haemorrhage.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Retinal Hemorrhage; Retrospective Studies; Vitreous Hemorrhage

In the aorta of prediabetic non-obese diabetic mice, a model of human type 1 diabetes, we investigated gene expression of the endothelin receptors and contractility to big endothelin-1 and endothelin-1 at the ages of 10 and 16 weeks. A subgroup of 10- week-old animals was treated with the endothelin ETA receptor antagonist LU461314 (30 mg/kg per day for 6 weeks). Blood glucose levels were normal in all animals. Real-time polymerase chain reaction analysis revealed that vascular ETB receptor expression was higher in 10-week-old non-obese diabetic (NOD) mice compared with controls. In 16-week-old NOD mice, but not in control mice, ETB receptor mRNA was twofold lower (P < 0.05 vs 10-week-old NOD mice). In all groups ETA receptor expression was unaffected by age or treatment. Contractions to big endothelin-1 and endothelin-1 were lower in 10-week-old NOD mice compared with controls. Treatment with LU461314 increased ETB receptor expression in 16-week-old NOD mice, but had no effect on vascular contractility. These data indicate that dysregulation of ETB receptor expression and a decreased contractile response to big endothelin-1 and endothelin-1 are present in the prediabetic state of a model of human type 1 diabetes. These alterations occur independent of glucose levels. Furthermore, ETA receptor blockade is effective in increasing ETB receptor gene expression, suggesting a potential role for endothelin ETA antagonists in the treatment of type 1 diabetes.

Topics: Age Factors; Animals; Aorta; Blood Glucose; Cardiovascular Agents; Diabetes Mellitus, Type 1; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelin A Receptor Antagonists; Endothelin-1; Female; Mice; Mice, Inbred NOD; Prediabetic State; Receptor, Endothelin A; Receptor, Endothelin B; RNA, Messenger; Up-Regulation; Vasoconstriction

To determine the extent to which cardiovascular therapies are prescribed in primary care for those with diabetes, compared with those without diabetes.. Population study of patients with and without diabetes identified using a national primary care prescribing database. All patients receiving a prescription for any diabetes therapy, including insulin and oral hypoglycaemic drugs, or diagnostic test kit for glucose ( n=8523) and those receiving no such therapies ( n=145,756) during a 1-year period (September 1999-August 2000) in the Eastern Regional Health Authority of Ireland were identified. In addition, a sub-set of patients receiving a nitrate prescription, a marker for ischaemic heart disease (IHD), were also identified ( n=14,826). Odds ratios and 95% confidence intervals for prescribing of cardiovascular therapies between those with diabetes and those without, adjusted for age and gender, were calculated using logistic regression.. The proportion of those (and 95% CES) with diabetes and IHD prescribed secondary preventative therapies was 37.3% (35.0, 39.6) for statins, 55.3% (53.0, 57.6) for angiotension converting enzyme inhibitors, 34.7% (32.5, 36.9) for beta blockers, 73.3% (71.2, 75.4) for aspirin, 4.4% (3.4, 5.4) for angiotensin-II antagonists and 2.5% (1.8, 3.2) for fibrates. The adjusted odds ratios for prescribing in those with diabetes compared with those without are 1.44 (1.30, 1.61) for statins, 3.09 (2.79, 3.42) for angiotension converting enzyme inhibitors, 0.82 (0.74, 0.91) for beta blockers, 1.23 (1.09, 1.38) for aspirin, 1.47 (1.13, 1.87) for angiotensin-II receptor blockers and 4.23 (2.88, 6.14) for lipid-lowering fibrates.. The greater rate of prescribing of cardiovascular therapies in those with diabetes relative to those without is not unexpected given the higher risk of coronary heart disease in those with diabetes. However, the proportion of patients with diabetes, particularly those with established IHD, prescribed cardiovascular therapies is considerably below that recommended in local and international guidelines.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Cardiovascular Diseases; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Prescriptions; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Myocardial Ischemia; Nitrates; Pharmacoepidemiology; Primary Health Care

To determine whether subsets of patients referred for a clinically indicated radionuclide adenosine stress study respond differently to a standard infusion of adenosine.. We assessed multiple clinical and hemodynamic variables in the first 2,000 patients who underwent adenosine perfusion studies in our laboratory. A relevant clinical variable was defined as one that was significantly associated with changes in heart rate and blood pressure during adenosine infusion. Relevant clinical variables that were most significantly related to hemodynamic variables included age, gender, rhythm (atrial fibrillation), diabetes, and left ventricular function. These variables were then related to symptomatic responses (adverse effects) to adenosine infusion. To determine whether the different peripheral responses to adenosine reflected clinically important differences in coronary vasodilatation, we compared perfusion imaging with coronary angiographic findings in the 408 patients who underwent both studies within 6 months of each other.. The decrease in systolic blood pressure was greater and the reflex tachycardia was less in patients 70 years of age or older and in those with insulin-dependent diabetes in comparison with younger patients and those without type 1 diabetes. Men had smaller decreases in blood pressure and smaller increases in heart rate than did women. Patients with atrial fibrillation and those with left ventricular ejection fraction less than 40% had smaller decreases in blood pressure and smaller increases in heart rate than did those in sinus rhythm or those with an ejection fraction of 40% or more. Age 70 years or older, male gender, atrial fibrillation, and left ventricular ejection fraction less than 40% were associated with fewer symptoms and less severe chest pain in comparison with patients without these variables. For patients with coronary angiograms, the relationship between coronary artery disease evident on angiography and perfusion abnormalities noted on scintigraphy was not different for any of the relevant clinical variables.. Common clinical patient subsets are associated with different peripheral hemodynamic and symptomatic responses to infusion of adenosine. Despite these observations, however, the ability to detect coronary artery disease with perfusion imaging is not obviously altered.

Topics: Adenosine; Age Factors; Aged; Atrial Fibrillation; Cardiovascular Agents; Coronary Angiography; Diabetes Mellitus, Type 1; Female; Hemodynamics; Humans; Linear Models; Logistic Models; Male; Multivariate Analysis; Retrospective Studies; Sex Factors; Tomography, Emission-Computed, Single-Photon; Ventricular Dysfunction, Left

The drug therapy prescribed for 412 diabetic patients attending an outpatient clinic over a 12 week period was recorded to try and identify potential therapeutic problems. Over 90% of the patients were prescribed at least one drug (including insulin) with oral hypoglycaemic agents prescribed for 86% of non-insulin requiring diabetics. 19% of patients were prescribed more than three drugs and few patients took drug combinations. Of patients prescribed either glibenclamide or chlorpropamide, 63% were aged 65 yr or older. Despite their potential adverse clinical and biochemical effects, diuretics and beta-blockers were commonly prescribed, especially in hypertension. The prescribing of "newer" anti-hypertensive drugs, combination products in patients taking a multiple drug regimen, and the potential dangers of sulphonylureas in the elderly are three areas where alteration of prescribing habits may be of value.

Topics: Adrenergic beta-Antagonists; Cardiovascular Agents; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diuretics; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Humans; Hypoglycemic Agents; Insulin; Medical Audit; Patient Compliance

Diabetes mellitus is a multifaceted disease which intervenes in the personal lives of those afflicted in many different ways. In this study prescription drug use among diabetics was analyzed in order to shed light on the characteristics of diabetic morbidity. Prescription drug use among diabetics and non-diabetics in a total population of 21,000 inhabitants in a defined geographic area were studied. The diabetic population was categorized according to the type of treatment received: insulin treatment, oral anti-diabetic treatment or dietary treatment or dietary treatment only. The pattern of prescription drug use differed between diabetics and non-diabetics and important differences were observed also between diabetics according to type of treatment. Drug use among those treated with insulin and those treated orally was substantially higher than among non-diabetics while the difference between diabetics on dietary regimen and non-diabetics was much smaller. All three treatment groups had considerably higher consumption of cardiovascular drugs than non-diabetics. Additional findings include more frequent antibiotic use among diabetics treated orally and on diet only than among non-diabetics. The use of these drugs was also common among insulin treated diabetics but did not differ significantly from among non-diabetics. Use of psychotropics was more common among diabetics treated with insulin and orally than among non-diabetics.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Cardiovascular Agents; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Prescriptions; Drug Utilization; Female; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Psychotropic Drugs; Regression Analysis; Sweden