Cardiovascular Disease In Diabetic Patients Research Articles

Similar cardiovascular risk factor profile in screen-detected and known type 2 diabetic subjects

Objective. To compare the cardiovascular disease (CVD) risk factor profile in subjects with screen-detected type 2 diabetes (SDM) and subjects with known type 2 diabetes (KDM). Design. Population-based, cross-sectional survey. Setting and subjects. In a single, semi-rural general practice 2082 subjects were between 20 and 69 years. Of those, 1970 subjects were invited, and a total of 1374 (69.7%) subjects were examined by blood tests, anthropometric measures, and self-administered questionnaires. Results. Before the survey 19 persons were known to have type 2 diabetes. The screening revealed another 31 individuals with type 2 diabetes, diagnosed according to the 1999 World Health Organization criteria. Age, levels of blood pressure, BMI, and dyslipidaemia, and markers of haemostasis and inflammation were comparable in the two groups. Median age in the KDM group was 58 vs. 57 years in the SDM group, p = 0.82, 79% were male vs. 61%, p = 0.23. In both groups 74% had blood pressure ≥ 130/85 mmHg, p = 1.00. In both groups 90% had BMI ≥ 25, p = 1.00, and about half in both groups had BMI ≥ 30, p = 0.56. In the KDM group 63% had dyslipidaemia (low HDL cholesterol or elevated triglycerides) vs. 80% in the SDM group, p = 0.32. Median levels of plasminogen-activator-inhibitor (PAI-1), tissue plasminogen activator (t-PA), as well as fibrinogen and C-reactive protein (CRP) were without statistically significant differences in the two groups, p > 0.1. In contrast, in markers of glycaemic regulation statistically significant differences were found between groups. Median HbA1 was 8.0 vs. 6.5, p < 0.001. Median fasting whole blood glucose level was 8.8 mmol/L vs. 6.3 mmol/L, p < 0.001, and glucose at two hours during OGTT was 16.9 mmol/L vs. 11.2 mmol/L, p < 0.001. Median fasting serum insulin level was 52 pmol/L vs. 80 pmol/L, p = 0.039 and at two hours 127 pmol/L vs. 479 pmol/L, p < 0.001. Conclusions. The CVD risk-factor profile of SDM patients was similar to the expected adverse profile of patients with KDM. This indicates an already increased risk of cardiovascular disease in diabetic patients before the diabetes becomes clinically manifest, supporting the need for early diagnosis.

Receptor Mediated Elevation in FABP4 Levels by Advanced Glycation End Products Induces Cholesterol and Triacylglycerol Accumulation in THP‐1 Macrophages

Excessive formation of advanced glycation end products (AGE) and lipid accumulation in macrophages play a pivotal role in the progression of atherosclerosis in diabetes mellitus. This study aimed to determine the molecular link between AGE-induced fatty acid binding protein 4 (FABP4) expression and macrophage lipid accumulation. AGE-BSA markedly increased macrophage FABP4 expression via engagement of RAGE, a 35-kDa transmembrane receptor that is able to bind extracellular AGE and responsible for the corresponding signal transduction, whereas knockdown of RAGE significantly reversed the FABP4 up-regulation. This effect was further paralleled with elevated intracellular total cholesterol and triacylglycerol levels. Finally, administration of FABP4 inhibitor totally abolished the increased lipid contents in response to AGE-BSA. These results indicate that FABP4 up-regulation is responsible for the enhanced macrophage lipid accumulation by AGE, which may underlie the accelerated formation of foam cells and development of atherosclerotic cardiovascular diseases in diabetic patients.

Prevalence of arterial and venous thromboembolic events in diabetic patients with and without the metabolic syndrome: A cross sectional study

Background Metabolic syndrome (MS) is associated with an increased risk of cardiovascular events. Recent studies have found a higher prevalence of the MS in patients with idiopathic venous thromboembolic events (VTE) compared to controls suggesting a role of the MS in the pathogenesis of VTE. The presence of MS was shown to further increase the risk of arterial cardiovascular diseases (CVD) in diabetic patients. Conversely, there are no studies that have compared the risk of VTE in diabetic patients with and without the MS. Methods A cross sectional study comparing the prevalence of arterial cardiovascular events and VTE in diabetic patients with and without the MS was conducted. Results Nine hundred and fifty three patients were included in the study; 85.7% of patients had MS. Patients with the MS had an increased prevalence of CVD as compared with those without (23.4% vs. 11.8%) and the MS was an independent predictor of CVD in diabetic patients (OR 3.16, 95%CI 1.78, 5.59) after multiple logistic regression analysis. The prevalence of VTE was higher in patients with the MS in comparison to patients without the MS, but this association was not statistically significant (3,43% vs 1.47%; OR 2.38, 95% CI 0.56, 10.10%). Conclusion Our study confirms the role of MS as an adjunctive cardiovascular risk factor in patients with diabetes. There is insufficient evidence to evaluate the role of the as an adjunctive risk factor for VTE in these patients. Further studies are necessary to confirm or refute these preliminary findings.

Effects of Intensive Blood Pressure Control in the Management of Patients With Type 2 Diabetes Mellitus in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial

To appreciate the importance of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial,1 one needs to remember that the systolic blood pressure (BP) target currently recommended by major guidelines for diabetic patients, that is, 130 mm Hg, except in the Appropriate Blood Pressure Control in Diabetes Study (ABCD) normotensive trial,7 which consisted of only a few hundred patients and had changes in creatinine clearance as the primary end point. Thus, ACCORD represents the only large-scale randomized trial that provides information on what happens to the cardiovascular risk of diabetic patients when SBP is reduced to 130 mm Hg as a result of randomization to the usual (rather than the tight) BP control treatment strategy. Thus, the message from ACCORD to guidelines and clinical practice is that in diabetic patients it is not necessary to adopt …

Cardiovascular Disease in Diabetes

Perspectives on the News commentaries are part of a free monthly CME activity. The Mount Sinai School of Medicine, New York, New York, designates this activity for 2.0 AMA PRA Category 1 credits. If you wish to participate, review this article and visit www.diabetes.procampus.net to complete a posttest and receive a certificate. The Mount Sinai School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians . This article is based on presentations addressing aspects of cardiovascular disease in diabetic patients at the American Diabetes Association's 67th Scientific Sessions, 22–26 June 2007, in Chicago, Illinois; at the 55th Annual Advanced Postgraduate Course, 1–3 February 2008, in San Francisco, California (the course is available online at http://professional.diabetes.org); and at the Mount Sinai Medical Center Diabetes Grand Rounds, 14 February 2008, in New York, New York. At a symposium on the evaluation of cardiac ischemia and macrovascular disease in patients with diabetes held at the American Diabetes Association (ADA) meeting, Theodore Mazzone (Chicago, IL) discussed approaches to subclinical ischemia in diabetes. There is a well-established relationship between diabetes and adverse outcome, as first demonstrated in the East-West Study of a Northern European population with a 3.5% 7-year cardiovascular disease (CVD) mortality rate among nondiabetic individuals without a history of myocardial infarction. Subjects with a history of myocardial infarction had an 18.8% risk, while those without a history of myocardial infarction but with a history of diabetes had a 20.2% 7-year risk (1), forming the basis of the argument that type 2 diabetes is a coronary artery disease (CAD) equivalent. Subsequent trials comparing diabetic patients without known CVD to nondiabetic patients with CVD, Mazzone stated, have confirmed that “the risk is pretty close in most populations.” Schramm et al. (abstract 692) presented an …

Cardiovascular diseases in diabetic patients

The review pays attention to a considerable rise in the incidence of diabetes mellitus (DM) and to its association with cardiovascular diseases (CVD) and events. It is noted that these events may be present much earlier than DM is diagnosed. The paper also discusses in detail a role of hyperglycemia, postprandial one in particular, hyperinsulinemia, insulin resistance, endothelial dysfunction, impaired blood rheological properties, lipid metabolic disturbances, and genetic and traditional risk factors in the development of atherosclerosis, coronary heart disease, chronic heart failure, cerebrovascular diseases, and lower extremity ischemia in DM.

Letter: Lack of Association between Serum Cystatin C Levels and Coronary Artery Disease in Diabetic Patients (Korean Diabetes J 2010;34:95-100).

Cardiovascular disease, including coronary artery disease (CAD), is the major cause of morbidity and mortality for individuals with diabetes and the largest contributor to the direct and indirect costs of diabetes [1,2]. Patients with diabetes are affected by other risk factors such as dyslipidemia, hypertension, prothrombic and proinflammatory factors, and therefore atherosclerosis in type 2 diabetes mellitus is often accelerated [3]. However, the pathophysiologic mechanisms responsible for the substantially increased risk for CAD in adult type 2 diabetes remain unclear. Inflammation plays a pivotal role in atherosclerosis, and inflammatory markers such as C-reactive protein, platelet-derived growth factor, transforming growth factor-beta, and granulocyte-macrophage colony stimulating factor may help clinicians to identify high risk patients [4,5]. In many previous studies, the association between inflammatory markers and coronary atherosclerosis was weak and mostly explained by the concomitant burden of CAD risk factors. Cystatin C is a novel endogenous marker of kidney function that may be more sensitive than inflammatory markers for detection of mild to moderate decrements in glomerular filtration rate [6]. However, few data exist on the relationship between serum cystatin C level and cardiovascular disease in diabetic patients with or without diabetic nephropathy. Maahs et al. [7] reported a significant relationship between serum cystatin C level and CAD in type 1 diabetic patients, but they assessed surrogate markers of CAD rather than CAD events or death and more importantly did not consider urinary albumin excretion. In contrast with previous studies, Kim et al. [8] reported that they found no association between serum cystatin C level and CAD in diabetic patients and that serum cystatin C levels were significantly higher in patients with diabetic nephropathy than in patients without both in CAD patients and non-CAD patients. However, the study used a retrospective case-control design, the sample was relatively small, and they did not evaluate the relationship between cystatin C levels and other markers (inflammatory, structural, and functional), body mass index (BMI) or other variables. Recently, Maahs et al. [9] investigated whether the relationship between cystatin C and progression of CAD differed between individuals with type 1 diabetes and without diabetes. In results, the univariate associations of cystatin C to CAD progression were similar in type 1 diabetic patients and without diabetes mellitus. The association of cystatin C to progression of CAD differed in the expected direction (increased cystatin C as a biomarker of worsening renal function associated with CAD progression) by type 1 diabetes status (P = 0.01) after adjustment for other risk factors of cardiovascular disease. Therefore, Maahs et al. [7] suggested, which a complex relationship exists among cystatin C, BMI, and CAD progression, which requires further study. I appreciate the devotion of study investigators, who are conducting important research about the relationship between cystatin C and diabetes, and hope that they will continue to do so in the future.

Relation between polymorphisms of receptor for advanced glycation end products (RAGE) and cardiovascular diseases in Chinese patients with diabetic nephropathy

Interaction of receptor for advanced glycation end products (RAGE) with advanced glycation end products (AGEs) is an important pathogenic mechanism of diabetic complications. Three mutations in the promoter region of the RAGE gene (T-429C, T-374A and a 63 bp deletion spanning from -407 to -345 nucleotides) were known to have increased transcriptional activities. We investigated the relationship between these polymorphisms and the risk of cardiovascular diseases in Chinese subjects with overt diabetic nephropathy. A total of 219 Type 2 diabetic subjects with nephropathy were recruited. Genotyping of the three polymorphisms in the genomic DNA was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients were followed for 8 years for the development of cardiovascular events and survival. The T-429 C and T-374 A polymorphism had no effect on the event-free survival of the subjects. For the 63 bp deletion polymorphism, the event-free survival was 37.0% and 63.2% at 96 months for del-/- and del-/+ genotypes, respectively (log-rank test, p = 0.034). After adjusting for confounders, the 63 bp deletion polymorphism had a marginal effect on event-free survival (adjusted hazard ratio: 3.517, 95% CI: 0.852 - 14.521, p = 0.082). Subjects without any mutation of the three polymorphisms have significantly higher risk of first ischemic heart disease than those with any of the three mutations (adjusted hazard ratio: 0.218, 95% CI: 0.062 - 0.764, p = 0.017). The 63 bp del-/+ genotype of the RAGE gene has a marginal benefit on the cardiovascular event-free survival in subjects with diabetic nephropathy. Subjects with any of the three mutations have a lower risk of ischemic heart disease. The role of RAGE in the pathogenesis of cardiovascular disease in diabetic patients requires further study.

Characteristics of sleep-disordered breathing in Japanese patients with type 2 diabetes mellitus

Sleep-disordered breathing (SDB), especially sleep apnea-hypopnea syndrome, is often observed in patients with type 2 diabetes mellitus; but there are only a few studies on SDB in Japanese diabetic subjects. We investigated the prevalence of SDB in diabetic patients; associations between severity of sleep apnea (SA) and clinical factors, visceral fat, and adiponectin; and associations between type of SA and clinical factors. In the present study, 40 Japanese diabetic patients underwent overnight cardiorespiratory monitoring, and night and morning measurements of serum adiponectin concentrations. Sleep apnea was detected in Japanese diabetic patients at a high prevalence (77.5%). The following variables were associated with SDB: age, body mass index, estimated visceral fat area, and nocturnal reduction in serum adiponectin concentrations. The prevalence of central sleep apnea (CSA, ≥5/h) was 32.3% among diabetic SDB patients. Diabetic SDB patients with CSA had higher hemoglobin, increased intima-media thickness, and higher plasma brain natriuretic peptide levels than those without CSA (<5/h). In conclusion, our study demonstrated a high prevalence of SDB in Japanese diabetic patients, which correlated with visceral fat area and adiponectin. A high frequency of CSA was noted in diabetic SDB patients, together with high hemoglobin, high brain natriuretic peptide, and increased intima-media thickness. The present results of prevalence of SDB may be relevant to the higher incidence of cardiovascular disease in diabetic patients, which need to be clarified in future studies.

Role of endothelial progenitor cells in diabetes mellitus

Endothelial progenitor cells (EPCs) are bone marrow-derived cells involved in endothelial healing and angiogenesis. EPCs are considered an integrated component of the cardiovascular system, which promotes vascular health. Derangement of EPC biology in diabetes has been hailed as a novel concept in the pathogenesis of micro- and macro-vascular complications. Additionally, EPCs are considered to be disease biomarkers, as they provide an index of cardiovascular risk. The mechanisms leading to EPC dysfunction in diabetes may include defective mobilization from bone marrow to peripheral blood and reduced half-life. Hyperglycemia is considered the major determinant of microvascular complications, while other mechanisms concur to increase the risk of cardiovascular disease in diabetic patients. EPCs may represent a novel pathophysiological connection to understand development and progression of diabetic complications.

Microvascular and macrovascular complications associated with diabetes in children and adolescents

Department of Pediatrics, Ulleval University˚Hospital, and Faculty of Medicine, University of Oslo, NorwayCorresponding author:Assoc. Prof. Kim DonaghueThe Children’s Hospital at Westmead, Locked Bag 4001,Westmead, NSW 2145, Australia.Tel: C61 2 9845 3172;fax: C61 2 9845 3170;e-mail: kimd@chw.edu.auAcknowledgments: Esko Wiltshire, Gisela Dahlquist, KennethLee Jones, Edna Roche, Amina Balafrej and Riccardo Bonfanti.Conflicts of interest: The authors have declared no conflictsof interest.Editors of the ISPAD Clinical Practice Consensus Guide-lines 2009 Compendium: Ragnar Hanas, Kim Donaghue,Georgeanna Klingensmith, and Peter Swift.This article is a chapter in the

Effect of metformin and folic acid on plasma homocysteine level in type 2 diabetic patients

Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease in diabetic patients. The aim of this study was to evaluate effects of metformin and folic acid on plasma homocysteine level in diabetic patients. In this clinical trial 47 new cases of type 2 diabetes were randomized to two groups. We treated patients in trial group with metformin and 1 mg folic acid, whereas patients in control group treated with metformin and placebo for 16 weeks. There was no significant difference in plasma homocysteine level and glycosylated hemoglobin (HbA1c) between two groups at the start of study. After 16 weeks plasma homocysteine level in the trial group did not change. In contrast plasma homocysteine level increased in the placebo group. There was significant difference in mean plasma homocysteine level between two groups (P-value < 0.01). This difference was highly significant in males (P-value < 0.0001). Correlation between glycosylated hemoglobin and plasma homocysteine level at start and end of study was not significant. This finding indicated that metformin increases plasma homocysteine level in diabetic patients especially males, whereas administration of folic acid with metformin can prevent this process.

THE EFFECT OF SOY PROTEIN WITH LOW CALORIE DIET ON BLOOD LIPIDS IN HYPERLIPIDEMIC TYPE 2 DIABETIC PATIENTS

ABSTRACT The effect of soy protein with low calorie diet on blood lipids in hyperlipidemic type 2 diabetic patients was studied. Thirty‐two subjects of both sexes, age range 25–65 years, were distributed in 16 cases and 16 controls. All subjects received a low calorie diet based on 1,400 kcal energy, 27% fat, 21% protein and 52% carbohydrate from a registered dietitian for 4 weeks. In addition to a low calorie diet, the case group received soy protein (30 g/d). Both groups significantly lost weight (P &lt; 0.001). Body mass index, waist and hip circumferences were significantly reduced (P &lt; 0.05) after 4 weeks of treatment. The difference between the groups was insignificant. In all subjects who were fasting, blood sugar significantly decreased (P &lt; 0.001). Soy protein was associated with a significant reduction in serum triacylglycerols (24.8%, P &lt; 0.05), whereas an insignificant reduction was seen in total cholesterol and low‐density lipoprotein (7.1 and 3.1%, respectively). No significant change occurred in high‐density lipoprotein cholesterol.PRACTICAL APPLICATIONSSerum lipid abnormalities are an established risk factor for cardiovascular disease in diabetic patients. Because of the side effects of long‐term medications in these patients, soy protein, as a part of healthy diet, may improve their lipid profile.

The Pleiotropic Effects of Simvastatin on Retinal Microvascular Endothelium Has Important Implications for Ischaemic Retinopathies

BackgroundCurrent guidelines encourage the use of statins to reduce the risk of cardiovascular disease in diabetic patients; however the impact of these drugs on diabetic retinopathy is not well defined. Moreover, pleiotropic effects of statins on the highly specialised retinal microvascular endothelium remain largely unknown. The objective of this study was to investigate the effects of clinically relevant concentrations of simvastatin on retinal endothelium in vitro and in vivo.Methods and FindingsRetinal microvascular endothelial cells (RMECs) were treated with 0.01–10 µM simvastatin and a biphasic dose-related response was observed. Low concentrations enhanced microvascular repair with 0.1 µM simvastatin significantly increasing proliferation (p<0.05), and 0.01 µM simvastatin significantly promoting migration (p<0.05), sprouting (p<0.001), and tubulogenesis (p<0.001). High concentration of simvastatin (10 µM) had the opposite effect, significantly inhibiting proliferation (p<0.01), migration (p<0.01), sprouting (p<0.001), and tubulogenesis (p<0.05). Furthermore, simvastatin concentrations higher than 1 µM induced cell death. The mouse model of oxygen-induced retinopathy was used to investigate the possible effects of simvastatin treatment on ischaemic retinopathy. Low dose simvastatin(0.2 mg/Kg) promoted retinal microvascular repair in response to ischaemia by promoting intra-retinal re-vascularisation (p<0.01). By contrast, high dose simvastatin(20 mg/Kg) significantly prevented re-vascularisation (p<0.01) and concomitantly increased pathological neovascularisation (p<0.01). We also demonstrated that the pro-vascular repair mechanism of simvastatin involves VEGF stimulation, Akt phosphorylation, and nitric oxide production; and the anti-vascular repair mechanism is driven by marked intracellular cholesterol depletion and related disorganisation of key intracellular structures.ConclusionsA beneficial effect of low-dose simvastatin on ischaemic retinopathy is linked to angiogenic repair reducing ischaemia, thereby preventing pathological neovascularisation. High-dose simvastatin may be harmful by inhibiting reparative processes and inducing premature death of retinal microvascular endothelium which increases ischaemia-induced neovascular pathology. Statin dosage should be judiciously monitored in patients who are diabetic or are at risk of developing other forms of proliferative retinopathy.

High glucose and interferon gamma synergistically stimulate MMP-1 expression in U937 macrophages by increasing transcription factor STAT1 activity

Recent diabetes control and complications trial and epidemiology of diabetes interventions and complications (DCCT/EDIC) and other clinical studies have reported that glucose control in patients with diabetes leads to a significant reduction of cardiovascular events and atherosclerosis, indicating that hyperglycemia plays an essential role in cardiovascular disease in diabetic patients. Although several mechanisms by which hyperglycemia promotes atherosclerosis have been proposed, it remains unclear how hyperglycemia promotes atherosclerosis by interaction with inflammatory cytokines. To test our hypothesis that hyperglycemia interplays with interferon gamma (IFNγ), a key factor involved in atherosclerosis, to up-regulate the expression of genes such as matrix metalloproteinases (MMPs) and cytokines that are involved in plaque destabilization, U937 macrophages cultured in medium containing either normal or high glucose were challenged with IFNγ and the expression of MMPs and cytokines were then quantified by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Results showed that high glucose and IFNγ had a synergistic effect on the expression of MMP-1, MMP-9 and IL-1β. High glucose also enhanced IFNγ-induced priming effect on lipopolysaccharide (LPS)-stimulated MMP-1 secretion. Furthermore, high glucose and IFNγ exert the synergistic effect on MMP-1 expression by enhancing STAT1 phosphorylation and STAT1 transcriptional activity. In summary, this study revealed a novel mechanism potentially involved in diabetes-promoted cardiovascular disease.

Cardiovascular Disease in Diabetes

Perspectives on the News commentaries are part of a free monthly CME activity. The Mount Sinai School of Medicine, New York, New York, designates this activity for 2.0 AMA PRA Category 1 credits. If you wish to participate, review this article and visit www.diabetes.procampus.net to complete a posttest and receive a certificate. The Mount Sinai School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians . This article is based on presentations addressing aspects of cardiovascular disease in diabetic patients at the American Diabetes Association's 67th Scientific Sessions, 22–26 June 2007, in Chicago, Illinois; at the 55th Annual Advanced Postgraduate Course, 1–3 February 2008, in San Francisco, California (the course is available online at http://professional.diabetes.org); and at the Mount Sinai Medical Center Diabetes Grand Rounds, 14 February 2008, in New York, New York. At a symposium on the evaluation of cardiac ischemia and macrovascular disease in patients with diabetes held at the American Diabetes Association (ADA) meeting, Theodore Mazzone (Chicago, IL) discussed approaches to subclinical ischemia in diabetes. There is a well-established relationship between diabetes and adverse outcome, as first demonstrated in the East-West Study of a Northern European population with a 3.5% 7-year cardiovascular disease (CVD) mortality rate among nondiabetic individuals without a history of myocardial infarction. Subjects with a history of myocardial infarction had an 18.8% risk, while those without a history of myocardial infarction but with a history of diabetes had a 20.2% 7-year risk (1), forming the basis of the argument that type 2 diabetes is a coronary artery disease (CAD) equivalent. Subsequent trials comparing diabetic patients without known CVD to nondiabetic patients with CVD, Mazzone stated, have confirmed that “the risk is pretty close in most populations.” Schramm et al. (abstract 692) presented an …

Primary Prevention of Cardiovascular Disease in People With Dysglycemia

Cardiovascular disease accounts for a great majority of deaths in patients with type 2 diabetes. According to the World Health Organization, the prevalence of cardiovascular disease in diabetic patients ranges from 26 to 36%. Fatality rate after myocardial infarction is greater in diabetic patients, and overall prognosis after coronary heart disease is worse. Based on these observations, it has been proposed that diabetes should be considered as a coronary heart disease risk equivalent. If that is the case, prevention of diabetes and early intervention should be pursued. This view is supported by the notion that cardiovascular risk is already increased in people with impaired glucose tolerance. Moreover, higher-than-optimum blood glucose is a major cause of cardiovascular mortality in most world regions of the world. Whether dysglycemia is a marker for a more complex metabolic condition or may directly contribute to excess cardiovascular risk is still a matter of debate. However, experimental work has shown how increased glucose level can trigger multiple mechanisms of susceptibility to atherosclerosis, and diabetes prevention trials have indicated that along with reduction of the rate of conversion toward diabetes, significant improvement in cardiovascular risk factors occurs. Moreover, in the STOP-NIDDM trial, targeting postprandial glucose was associated with reduction in new cases of hypertension, myocardial infarction, and any cardiovascular events. In conclusion, dysglycemia should be included in the list of established cardiovascular risk factors and early treatment introduced in the attempt to improve cardiovascular morbidity and mortality.

Anaemia and kidney dysfunction in Caribbean Type 2 diabetic patients

BackgroundAnaemia has been shown in previous studies to be a risk factor for cardiovascular disease in diabetic patients with chronic kidney disorder. This study was aimed to assess the prevalence of anaemia and kidney dysfunction in Caribbean type 2 diabetic patients that have been previously shown to have a high prevalence of the metabolic syndrome.Methods155 type 2 diabetic patients and 51 non-diabetic subjects of African origin were studied. Anthropometric parameters were measured and fasting blood samples were collected for glucose, creatinine, glycated hemoglobin and complete blood count. Anaemia was defined as haemoglobin < 12 g/dl (F) or < 13 g/dl (M). Kidney function was assessed using glomerular filtration rate (GFR) as estimated by the four-variable Modification of Diet in Renal Disease (MDRD) study equation. Subjects were considered to have chronic kidney disease when the estimated GFR was < 60 ml/min per 1.73 m2. Comparisons for within- and between-gender, between diabetic and non-diabetic subjects were performed using Student's t-test while chi-square test was employed for categorical variables.ResultsThe diabetic patients were older than the non-diabetic subjects. While male non-diabetic subjects had significantly higher red blood cell count (RBC), haemoglobin and hematocrit concentrations than non-diabetic female subjects (p < 0.001), the RBC and hematocrit concentrations were similar in male and female diabetic patients. Furthermore, irrespective of gender, diabetic patients had significantly higher prevalence rate of anemia than non-diabetic subjects (p < 0.05). Anaemic diabetes patients had significantly lower GFR (67.1 ± 3.0 vs. 87.9 ± 5.4 ml/min per 1.73 m2, p < 0.001) than non-anaemic patients.ConclusionA high prevalence of anaemia was identified in this group of type 2 diabetic patients previously shown to have a high prevalence of the metabolic syndrome. It is therefore recommended that diagnostic laboratories in developing countries and elsewhere should include complete blood count in routine laboratory investigations in the management of diabetic patients.

Diabetic HDL-associated myristic acid inhibits acetylcholine-induced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin

In the current study, we examined whether diabetes affected the ability of HDL to stimulate nitric oxide (NO) production. Using HDL isolated from both diabetic humans and diabetic mouse models, we found that female HDL no longer induced NO synthesis, despite containing equivalent amounts of estrogen as nondiabetic controls. Furthermore, HDL isolated from diabetic females and males prevented acetylcholine-induced stimulation of NO generation. Analyses of both the human and mouse diabetic HDL particles showed that the HDLs contained increased levels of myristic acid. To determine whether myristic acid associated with HDL particles was responsible for the decrease in NO generation, myristic acid was added to HDL isolated from nondiabetic humans and mice. Myristic acid-associated HDL inhibited the generation of NO in a dose-dependent manner. Importantly, diabetic HDL did not alter the levels of endothelial NO synthase or acetylcholine receptors associated with the cells. Surprisingly, diabetic HDL inhibited ionomycin-induced stimulation of NO production without affecting ionomycin-induced increases in intracellular calcium. Further analysis indicated that diabetic HDL prevented calmodulin from interacting with endothelial NO synthase (eNOS) but did not affect the activation of calmodulin kinase or calcium-independent mechanisms for stimulating eNOS. These studies are the first to show that a specific fatty acid associated with HDL inhibits the stimulation of NO generation. These findings have important implications regarding cardiovascular disease in diabetic patients.

Use of aspirin for primary and secondary prevention of cardiovascular disease in diabetic patients in an ambulatory care setting in Spain.

BackgroundThis study was conducted in order to determine the use of aspirin and to assess the achievement of therapeutic targets in diabetic patients according to primary (PP) or secondary prevention (SP).MethodsThis is a retrospective, observational study including patients ≥18 years with diabetes mellitus followed in four primary care centers. Measurements included demographics, use of aspirin and/or anticoagulant drugs, co-morbidities, clinical parameters and proportion of patient at therapeutic target (TT). Descriptive statistics, chi-square test and logistic regression model were used for significance.ResultsA total of 4,140 patients were analyzed, 79.1% (95% confidence intervals [CI]: 77.7–80.5%) in PP and 20.9% (95% CI: 18.2–23.7%) in SP. Mean age was 64.1 (13.8) years, and 49.3% of patient were men (PP: 46.3, SP: 60.7, p = 0.001). Aspirin was prescribed routinely in 20.8% (95% CI: 19.4–22.2%) in PP and 60.8% (95% CI: 57.6–64.0%) in SP. Proportion of patient at TT was 48.0% for blood pressure and 59.8% for cholesterol. Use of aspirin was associated to increased age [OR = 1.01 (95% CI: 1.00–1.02); p = 0.011], cardiovascular-risk factors [OR = 1.14 (95% CI: 1.03–1.27); p = 0.013], LDL-C [OR = 1.42 (95% CI: 1.06–1.88); p = 0.017] and higher glycated hemoglobin [OR = 1.51 (95% CI: 1.22–1.89); p = 0.000] were covariates associated to the use of aspirin in PP.ConclusionTreatment with aspirin is underused for PP in patients with diabetes mellitus in Primary Care. Achievement of TT should be improved.