Cardiovascular Diabetology - Latest Articles

Comparative effect of angiotensin II type I receptor blockers and calcium channel blockers on laboratory parameters in hypertensive patients with type 2 diabetes

Yayoi Nishida — 2012-05-17T00:00:00Z

Background: Both angiotensin II type I receptor blockers (ARBs) and calcium channel blockers (CCBs) are widely used antihypertensive drugs. Many clinical studies have demonstrated and compared the organ-protection effects and adverse events of these drugs. However, few large-scale studies have focused on the effect of these drugs as monotherapy on laboratory parameters. We evaluated and compared the effects of ARB and CCB monotherapy on clinical laboratory parameters in patients with concomitant hypertension and type 2 diabetes mellitus. Methods: We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and July 31, 2011, to identify cohorts of new ARB users (n = 601) and propensity-score matched new CCB users (n = 601), with concomitant mild to moderate hypertension and type 2 diabetes mellitus. We used a multivariate-adjusted regression model to adjust for differences between ARB and CCB users, and compared laboratory parameters including serum levels of triglyceride (TG), total cholesterol (TC), non-fasting blood glucose, hemoglobin A1c (HbA1c), sodium, potassium, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), hemoglobin and hematocrit, and white blood cell (WBC), red blood cell (RBC) and platelet (PLT) counts up to 12 months after the start of ARB or CCB monotherapy. Results: We found a significant reduction of serum TC, HbA1c, hemoglobin and hematocrit and RBC count and a significant increase of serum potassium in ARB users, and a reduction of serum TC and hemoglobin in CCB users, from the baseline period to the exposure period. The reductions of RBC count, hemoglobin and hematocrit in ARB users were significantly greater than those in CCB users. The increase of serum potassium in ARB users was significantly greater than that in CCB users. Conclusions: Our study suggested that hematological adverse effects and electrolyte imbalance are greater with ARB monotherapy than with CCB monotherapy.

Associations between retinol-binding protein 4 and cardiometabolic risk factors and subclinical atherosclerosis in recently postmenopausal women: Cross-sectional analyses from the KEEPS Study

Gary Huang — 2012-05-15T00:00:00Z

Background: The published literature regarding the relationships between retinol-binding protein 4 (RBP4) and cardiometabolic risk factors and subclinical atherosclerosis is conflicting, likely due, in part, to limitations of frequently used RBP4 assays. Prior large studies have not utilized the gold-standard Western Blot analysis of RBP4 levels. Methods: Full-length serum RBP4 levels were measured by Western Blot in 709 postmenopausal women screened for the Kronos Early Estrogen Prevention Study. Cross-sectional analyses related RBP4 levels to cardiometabolic risk factors, carotid artery intima-media thickness (CIMT), and coronary artery calcification (CAC). Results: The mean age of women was 52.9 (+/- 2.6) years, and the median RBP4 level was 49.0 (interquartile range 36.9-61.5) ug/mL. Higher RBP4 levels were weakly associated with higher triglycerides (age, race, and smoking-adjusted partial Spearman correlation coefficient= 0.10; P=0.01), but were unrelated to blood pressure, cholesterol, C-reactive protein, glucose, insulin, and CIMT levels (all partial Spearman correlation coefficients [less than or equal to]0.06, P>0.05). Results suggested a curvilinear association between RBP4 levels and CAC, with women in the bottom and upper quartiles of RBP4 having higher odds of CAC (odds ratio [95% confidence interval] 2.10 [1.07-4.09], 2.00 [1.02-3.92], 1.64 [0.82-3.27] for the 1st, 3rd, and 4th RBP4 quartiles vs. the 2nd quartile). However, a squared RBP4 term in regression modeling was non-significant (P=0.10). Conclusions: In these healthy, recently postmenopausal women, higher RBP4 levels were weakly associated with elevations in triglycerides and with CAC, but not with other risk factors or CIMT. These data using the gold standard of RBP4 methodology only weakly support the possibility that perturbations in RBP4 homeostasis may be an additional risk factor for subclinical coronary atherosclerosis.Trial Registration: ClinicalTrials.gov number NCT00154180

Gender difference in carotid intima-media thickness in type 2 diabetic patients: a 4-year follow-up study

Bo Zhao — 2012-05-14T00:00:00Z

Background: Different population studies have reported gender difference in carotid intima-media thickness (CIMT), which is proved to be a risk factor of cardiovascular diseases. However, few longitudinal researches examine this gender difference in type 2 diabetes mellitus (T2DM) patients. Therefore, we prospectively analyzed CIMT in T2DM patients over a 4-year follow-up period. Methods: 355 T2DM patients (mean age 59 years; 54.9% women) were included in the present study. CIMT were measured using Color Doppler ultrasound. CIMT was measured at baseline (CIMT) in 2006 and at follow-up in 2010. Biochemical and clinical measurements were collected at baseline. Results: Mean value of CIMT1 and CIMT2 were 0.740+/-0.148mm and 0.842+/-0.179mm, respectively. Men had higher CIMT than women both at baseline and at follow-up (CIMT1: 0.762+/-0.149 vs 0.723+/-0.146 mm, P=0.0149; CIMT2: 0.880+/-0.189 vs 0.810+/-0.164 mm, P=0.0002). Mean annual progression of CIMT (dCIMT) was 0.025+/-0.022 mm/year. dCIMT was larger in men than in women (0.030+/-0.025 vs 0.022+/-0.019 mm, P=0.0006). In multiple regression analyses, age was an independent risk factor of CIMT in both genders, while dCIMT was associated with age only in men. Conclusions: Gender difference in CIMT was confirmed in T2DM patients. Moreover, impact of ageing on CIMT progression only existed in men, which might be the reason that gender difference in CIMT increased with age.

Blood pressure and lipid management fall far short in persons with type 2 diabetes: Results from the DIAB-CORE Consortium including six German population-based studies

Ina-Maria Rückert — 2012-05-08T00:00:00Z

Background Although most deaths among patients with type 2 diabetes (T2D) are attributable to cardiovascular disease, modifiable cardiovascular risk factors appear to be inadequately treated in medical practice. The aim of this study was to describe hypertension, dyslipidemia and medical treatment of these conditions in a large population-based sample.Methods The present analysis was based on the DIAB-Core project, in which data from five regional population-based studies and one nationwide German study were pooled. All studies were conducted between 1997 and 2006. We assessed the frequencies of risk factors and co-morbidities, especially hypertension and dyslipidemia, in participants with and without T2D. The odds of no or insufficient treatment and the odds of pharmacotherapy were computed using multivariable logistic regression models. Types of medication regimens were described.Results The pooled data set comprised individual data of 15,071 participants aged 45-74 years, including 1287 (8.5%) participants with T2D.Subjects with T2D were significantly more likely to have untreated or insufficiently treated hypertension, i.e. blood pressure of >= 140/90 mmHg (OR = 1.43, 95% CI 1.26-1.61) and dyslipidemia i.e. a total cholesterol/HDL-cholesterol ratio >= 5 (OR = 1.80, 95% CI 1.59-2.04) than participants without T2D.Untreated or insufficiently treated blood pressure was observed in 48.9% of participants without T2D and in 63.6% of participants with T2D. In this latter group, 28.0% did not receive anti-hypertensive medication and 72.0% were insufficiently treated.In non-T2D participants, 28.8% had untreated or insufficiently treated dyslipidemia. Of all participants with T2D 42.5% had currently elevated lipids, 80.3% of these were untreated and 19.7% were insufficiently treated.Conclusions Blood pressure and lipid management fall short especially in persons with T2D across Germany. The importance of sufficient risk factor control besides blood glucose monitoring in diabetes care needs to be emphasized in order to prevent cardiovascular sequelae and premature death.

Ginkgo biloba extract reduces high-glucose-induced endothelial adhesion by inhibiting the redox-dependent interleukin-6 pathways

Jia-Shiong Chen — 2012-05-03T00:00:00Z

Background: Chronic elevation of glucose level activates vascular inflammation and increases endothelial adhesiveness to monocytes, an early sign of atherogenesis. This study aimed to elucidate the detailed mechanisms of high-glucose-induced endothelial inflammation, and to investigate the potential effects of Ginkgo biloba extract (GBE), an antioxidant herbal medicine, on such inflammation.Materials and methods: Human aortic endothelial cells were cultured in high glucose or mannitol as osmotic control for 4 days. The expression of cytokines and adhesion molecules and the adhesiveness of endothelial cells to monocytes were examined. The effects of pretreatment of GBE or N-acetylcysteine, an antioxidant, were also investigated. Results: Either high glucose or mannitol significantly increased reactive oxygen species (ROS) production, interleukin-6 secretion, intercellular adhesion molecule-1 (ICAM-1) expression, as well as endothelial adhesiveness to monocytes. The high-glucose-induced endothelial adhesiveness was significantly reduced either by an anti-ICAM-1 antibody or by an interleukin-6 neutralizing antibody. Interleukin-6 (5 ng/ml) significantly increased endothelial ICAM-1 expression. Piceatannol, a signal transducer and activator of transcription (STAT) 1/3 inhibitor, but not fludarabine, a STAT1 inhibitor, suppressed high-glucose-induced ICAM-1 expression. Pretreatment with GBE or N-acetylcysteine inhibited high-glucose-induced ROS, interleukin-6 production, STAT1/3 activation, ICAM-1 expression, and endothelial adhesiveness to monocytes. Conclusions: Long-term presence of high glucose induced STAT3 mediated ICAM-1 dependent endothelial adhesiveness to monocytes via the osmotic-related redox-dependent interleukin-6 pathways. GBE reduced high-glucose-induced endothelial inflammation mainly by inhibiting interleukin-6 activation. Future study is indicated to validate the antioxidant/anti-inflammatory strategy targeting on interleukin-6 for endothelial protection in in vivo and clinical hyperglycemia.

Expression of fourteen novel obesity-related genes in Zucker diabetic fatty rats

Peter Schmid — 2012-05-03T00:00:00Z

Background: Genome-wide association studies (GWAS) are useful to reveal an association between single nucleotide polymorphisms and different measures of obesity. A multitude of new loci has recently been reported, but the exact function of most of the according genes is not known. The aim of our study was to start elucidating the function of some of these genes. Methods: We performed an expression analysis of fourteen genes, namely BDNF, ETV5, FAIM2, FTO, GNPDA2, KCTD15, LYPLAL1, MCR4, MTCH2, NEGR1, NRXN3, TMEM18, SEC16B and TFAP2B, via real-time RT-PCR in adipose tissue of the kidney capsule, the mesenterium and subcutaneum as well as the hypothalamus of obese Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats at an age of 22 weeks. Results: All of our target genes except for SEC16B showed the highest expression in the hypothalamus. This suggests a critical role of these obesity-related genes in the central regulation of energy balance. Interestingly, the expression pattern in the hypothalamus showed no differences between obese ZDF and lean ZL rats. However, LYPLAL1, TFAP2B, SEC16B and FAIM2 were significantly lower expressed in the kidney fat of ZDF than ZL rats. NEGR1 was even lower expressed in subcutaneous and mesenterial fat, while MTCH2 was higher expressed in the subcutaneous and mesenterial fat of ZDF rats. Conclusion: The expression pattern of the investigated obesity genes implies for most of them a role in the central regulation of energy balance, but for some also a role in the adipose tissue itself. For the development of the ZDF phenotype peripheral rather than central mechanisms of the investigated genes seem to be relevant.

In-hospital death in acute coronary syndrome was related to admission glucose in men but not in women

Julio Takada — 2012-05-03T00:00:00Z

Background: Admission hyperglycaemia is associated with mortality in patients with acute coronary syndrome (ACS), but controversy exists whether hyperglycaemia uniformly affects both genders. We evaluated coronary risk factors, gender, hyperglycaemia and their effect on hospital mortality. Methods: 959 ACS patients (363 women and 596 men) were grouped based on glycaemia ≥ or < 200 mg/dL and gender: men with glucose < 200 mg/dL (menG-); women with glucose < 200 mg/dL (womenG-); men with glucose ≥ 200 mg/dL (menG+); and women with glucose ≥ 200 mg/dL (womenG+). A logistic regression analysis compared the relation between gender and glycaemia groups and death, adjusted for coronary risk factors and laboratory data.Results groupmenG- had lower mortality than menG + (OR = 0.172, IC95% 0.062-0.478), and womenG + (OR = 0.275, IC95% 0.090-0.841); womenG- mortality was lower than menG + (OR = 0.230, IC95% 0.074-0.717). No difference was found between menG + vs womenG + (p = 0.461), or womenG- vs womenG + (p = 0.110). Age (OR = 1.067, IC95% 1.031–1.104), EF (OR = 0.942, IC95% 0.915-0.968), and serum creatinine (OR = 1.329, IC95% 1.128-1.566) were other independent factors related to in-hospital death. Conclusions: Death was greater in hyperglycemic men compared to lower blood glucose men and women groups, but there was no differences between women groups in respect to glycaemia after adjustment for coronary risk factors.

Advanced glycation end products impair the migration, adhesion and secretion potentials of late endothelial progenitor cells

Hong Li — 2012-04-30T00:00:00Z

Background: Endothelial progenitor cells (EPCs), especially late EPCs, play a critical role in endothelialmaintenance and repair, and postnatal vasculogenesis. Advanced glycation end products(AGEs) have been shown to impair EPC functions, such as proliferation, migration andadhesion. However, their role in the regulation of the production of vasoactive substances inlate EPCs is less well defined.MethodsPassages of 3~5 EPCs, namely late EPCs, were cultured with different concentrations (0~500mug/ml) of AGEs, and the apoptosis, adhesion and migration were subsequently determined.The release of vasoactive substances, such as stromal cell-derived factor-1 (SDF-1), nitricoxide (NO), prostaglandin I2 (PGI2), plasminogen activator inhibitor-1 (PAI-1), tissueplasminogen activator (tPA), and in addition the activity of superoxide dismutase (SOD),were evaluated by ELISA. At the same time, the gene and protein expressions of CXCR4were assayed by real-time RT-PCR and western-blot. Results: AGEs promoted late EPC apoptosis. Moreover, AGEs impaired late EPC migration andadhesion in a concentration-dependent manner. Accordingly, the production of SDF-1 wasdecreased by AGEs. Although the CXCR4 expressions of late EPCs were up-regulated forAGE concentrations of 50, 100 or 200 mug/ml, a marked decrease was observed for the higherconcentration of 500 mug/ml. Furthermore, co-culturing with AGEs decreased the levels ofNO, t-PA, PGI2, and the activity of SOD but up-regulated the production of PAI-1. Conclusion: Our data provide evidence that AGEs play an important role in impairing late EPC functions,which could contribute to the development of vascular diseases in diabetes.

Mammalian Target of Rapamycin Signaling in Diabetic Cardiovascular Disease

Zhao Chong — 2012-04-30T00:00:00Z

Diabetes mellitus currently affects more than 170 million individuals worldwide and is expected to afflict another 200 million individuals in the next 30 years. Complications of diabetes as a result of oxidant stress affect multiple systems throughout the body, but involvement of the cardiovascular system may be one of the most severe in light of the impact upon cardiac and vascular function that can result in rapid morbidity and mortality for individuals. Given these concerns, the signaling pathways of the mammalian target of rapamycin (mTOR) offer exciting prospects for the development of novel therapies for the cardiovascular complications of diabetes. In the cardiovascular and metabolic systems, mTOR and its multi-protein complexes of TORC1 and TORC2 regulate insulin release and signaling, endothelial cell survival and growth, cardiomyocyte proliferation, resistance to beta-cell injury, and cell longevity. Yet, mTOR can, at times, alter insulin signaling and lead to insulin resistance in the cardiovascular system during diabetes mellitus. It is therefore vital to understand the complex relationship mTOR and its downstream pathways hold during metabolic disease in order to develop novel strategies for the complications of diabetes mellitus in the cardiovascular system.

Vascular memory: can we broaden the concept of the metabolic memory?

György Jermendy — 2012-04-30T00:00:00Z

Based on the results of recent randomized, controlled clinical trials and analyses of their follow-up periods the concept of metabolic memory cannot be restricted to antihyperglycaemic treatment only, rather it can be extended to lipid-lowering and antihypertensive treatment and even life-style modification. This broadened concept can be designated as vascular memory. According to this new concept, not only immediate and short-term but long-term effects of the metabolic and cardiovascular risk milieu are of great importance. Consequently, early and intensive lifestyle interventions, treatment of hyperglycaemia, lipid abnormalities and hypertension can result in beneficial effects on cardiovascular outcomes even in the long run. On the contrary, failing in target-oriented treatment from early detection of abnormalities can be associated with life-threatening cardiovascular events subsequently. Additional experimental studies are needed to characterize the exact pathomechanism of vascular memory and further clinical trials are also essential to explore its real clinical significance.