No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Prevalence of cardiovascular disease and risk factors in a type 2 diabetic population of the North Catalonia diabetes study
Abstract
Purpose: The purpose of the study was to evaluate the prevalence of cardiovascular disease (CVD), cardiovascular risk factors (CVRFs), and their control in patients with type 2 diabetes mellitus (T2DM) at primary care settings from the North Catalonia Diabetes Study (NCDS).
Data sources: In this multicentre cross-sectional descriptive study, data were collected from a random sample of 307 patients with T2DM. The prevalence of CVD, CVRF, metabolic syndrome (MS), coronary heart disease (CHD) risk at 10 years (Framingham Point Scores), and CVRF control was evaluated. MS and lipid profiles were established according to Adult Treatment Panel III criteria.
Conclusions: CVD prevalence was 22.0% (CHD: 18.9% and peripheral ischemia: 4.5%) and more frequent in men. The prevalence of selected CVRF was: hypertension: 74.5%; dyslipidemia: 77.7%; smoking: 14.9%; obesity 44.9%, and familial CVD: 38.4%. Three or more CVRFs, including T2DM, were observed in 91.3%. MS prevalence was 68.7%. Framingham score was 10.0%, higher in men than in women. CVD prevalence was related to: age, number of CVRFs, duration of diabetes, familial history of CVD, waist circumference, hypertension, lipid profile, kidney disease, and Framingham score, but not to MS by itself. Correct lipid profiles and blood pressure were only observed in 18.9% and 24.0%, respectively, whereas platelet aggregation inhibitors were only recorded in 16.1% of the patient cohort. MS presence was not an independent risk factor of CVD in our study.
Implications for practice: The high prevalence of CVD and an inadequate control of CVRF, which were apparent in the NCDS population, would suggest that advanced practice nurses should consider incorporating specific cardiovascular assessment in their routine care of persons with T2DM.
... This was significantly higher than in the southern region of Saudi Arabia where Alavudeen et al. (2013) stated that HTN among only 24.71% of patients with DM-II [24]. On the other hand, global studies had a higher prevalence estimated at 60.25%, 74.5% and 77.6% in Egypt, north Catalonia and Sri Lanka respectively [17,26,27]. ...
Background
Diabetes mellitus is considered a major risk factor for cardiovascular diseases. Patients with diabetes mellitus type 2 (DM-II) are at twice as high risk for the development of cardiovascular diseases than the general population. Thus, we aimed to assess the most prevalent cardiovascular risk (CVR) factors among DM-II patients in the Eastern province of Saudi Arabia.
Method
This is a cross-sectional, retrospective, and observational study conducted on DM-II patients at King Fahad University Hospital (KFUH) Al Khobar, Saudi Arabia, from January 2016 to December 2021. The total number of participants was 373 who were patients with DM-II. The patients' demographic information (age, sex, marital status, height, weight, body mass index (BMI), waist, hip circumference, and waist-hip ratio were calculated or obtained from hospital electronic records as were the CVR factors, age, gender, smoking habits, physical activity, BMI, haemodynamic measurements, glycosylated haemoglobin (HbA1C) levels and lipid profile.
The collected data were analyzed by using SPSS Statistics v.28 (IBM Corp., Armonk, NY). The descriptive statistics were reported using mean±SD for numerical data and relative frequencies (%) for categorical data. P < 0.05 were counted significant. Quantitative data were analyzed using the ANOVA test to compare the means of the three groups. Qualitative data were analyzed and compared using the chi-square test. Fisher’s exact test was also used to study the statistical significance of variables. Spearman rank correlation was used to study the relationship between HbA1C and other CV risk factors.
Results
The mean age was 58 (± 13) years; females were 57% of the sample. Around 92% were smokers, 84% had a sedentary lifestyle, 72% had dyslipidemia, 58% were obese, 30% were overweight, 58% reported poorly control of their diabetes, 50% had hypertension and 32% had pre-hypertension. Furthermore, 89% of participants had two or more CVR factors other than DM-II. We found a significant association between high body mass index, dyslipidemia, high systolic blood pressure and pulse pressure (p<0.05) with HbA1C.
Conclusion
The majority of participants had two or more cardiovascular risk factors in addition to DM-II. Poor control of DM-II and cardiovascular risk factors cannot be ignored and primary to tertiary prevention must be the top priority when managing the diabetic population in order to prevent devastating outcomes and progression of reversible morbidity.
... 24 A study in Saudi Arabia reported that over 78% of diabetic patients only suffered from hypertension. 25 In contrast, some other studies have reported a lower prevalence of CVD comorbidity with diabetes, 26,27 which could be attributed to the absence of hypertension as a separate classification of CVD complications. According to a recent systematic review, 8 most studies have classified hypertension as part of CVD rather than a separate comorbid condition. ...
Background:
Cardiovascular disease (CVD) is the most prevalent comorbid condition among patients with diabetes. The objective of this study is to determine the incremental healthcare resource utilization and expenditures (HRUE) associated with CVD comorbidity in diabetic patients.
Methods:
In a cross-sectional study, patients receiving antidiabetic drugs were identified using the 2014 database of the Iran Health Insurance Organization of East Azerbaijan province (Iran). The frequency of HRUE was the main outcome. Outcome measures were compared between diabetic patients with and without CVD comorbidity during 2014-2016. The generalized regression model was used to adjust for cofounders because of a highly skewed distribution of data. Negative binomial regression and gamma distribution model were applied for the count and expenditure data, respectively.
Results:
A total of 34,716 diabetic patients were identified, of which 21,659 (63%) had CVD comorbidity. The incremental healthcare resource utilization associated with CVD compared to non-CVD diabetic patients for physician services, prescription drugs, laboratory tests, and medical imaging was 5.9±0.34 (28% increase), 46±1.9 (46%), 12.9±0.66 (27%), and 0.16±0.40 (7%), respectively (all P<0.001). Similarly, extra health care costs associated with CVD comorbidity for physician services, prescription drugs, laboratory tests, and medical imaging were 10.6±0.67 million IRR (294.4±18.6 USD) (50% increase), 1.44±0.06 million IRR (40±1.6 USD) (32%), 8.36±0.57 million IRR (232.2±15.8 USD) (58%), 0.51±0.02 million IRR (14.1±0.5 USD) (24%), and 0.29±0.02 million IRR (8±0.5 USD) (22%), respectively (all P<0.001).
Conclusion:
CVD comorbidity substantially increases HRUE in patients with diabetes. Our findings draw the attention of healthcare decision-makers to proactively prevent CVD comorbidity in diabetic patients.
... The results showed that the prevalence of CVD and insufficient control of CVD risk factors among our patients were high. These findings are in agreement with other studies in different regions (27,28). More aggressive interventions are crucial for patients with diabetes mellitus, including better patient education and more aggressive control of glycaemia, hypertension, hyperlipidemia, and metabolic syndrome. ...
Background/aim: Diabetes mellitus is a risk factor for cardiovascular diseases (CVDs), which are among the major causes of deaths in type 2 diabetes (T2D). The purpose of the present study was to determine the association of C282Y and H63D mutations in the HFE gene with increased risk of coronary artery disease (CAD) in T2D patients. Materials and methods: Two hundred and ninety individuals were divided into two groups: a case group and a control group. Genomic DNA of peripheral venous blood cells was extracted and the HFE gene mutations were analyzed using the PCR–RFLP technique. Results: Data analysis revealed a significant difference between the allele frequencies of H63D and C282Y mutations between the case group and the controls (P < 0.05). The relationships between the GA and GG genotypes in C282Y and H63D mutations in terms of fasting blood sugar (FBS), lipid profile (total cholesterol, triglycerides, high-density lipoproteins (HDL), low-density lipoproteins), body mass index (BMI), HbA1c, micro albuminuria, and creatine levels did not show a significant differences between the two groups (P > 0.05). Using a logistic regression model, BMI, FBS, HDL, and total cholesterol levels were significantly different with independent predictors of CVD (P < 0.05). Conclusion: Our results revealed a significant correlation between C282Y and H63D mutations and the development of CAD in T2D patients
Cardiovascular and related metabolic diseases are significant global health challenges. Glucagon-like peptide 1 (GLP-1) is a brain-gut peptide secreted by ileal endocrine that is now an established drug target in type 2 diabetes (T2DM). GLP-1 targeting agents have been shown not only to treat T2DM, but also to exert cardiovascular protective effects through regulating multiple signaling pathways. The mitogen-activated protein kinase (MAPK) pathway, a common signal transduction pathway for transmitting extracellular signals to downstream effector molecules, is involved in regulating diverse cell physiological processes, including cell proliferation, differentiation, stress, inflammation, functional synchronization, transformation and apoptosis. The purpose of this review is to highlight the relationship between GLP-1 and cardiovascular disease (CVD), and discuss how GLP-1 exerts cardiovascular protective effects through MAPK signaling pathway. This review also discusses the future challenges in fully characterizing and evaluating the CVD protective effects of GLP-1 receptor agonists (GLP-1RA) at the cellular and molecular level. A better understanding of MAPK signaling pathway that are disregulated in CVD may aid in the design and development of promising GLP-1RA.
IntroductionCardiovascular disease (CVD) is a leading cause of morbidity and mortality in people with type 2 diabetes mellitus (T2DM). The objectives of this systematic literature review were to identify and synthesize published data describing the epidemiology and mortality of CVD in the T2DM population and the associated economic burden.Methods
We conducted a systematic review searching the PubMed and MEDES databases from 2009 to 2019 using predefined selection criteria. Peer-reviewed observational studies reporting primary or secondary data on CVD prevalence, incidence, mortality, resource use and costs in patients with T2DM in Spain, written in English and Spanish, were included. Data were tabulated and summarized descriptively.ResultsOf 706 articles identified, 52 were included in the review. Most studies were based on data from hospital discharge databases and registries. The reported prevalence of CVD among patients with T2DM ranged from 6.9 to 40.8%. The prevalence of coronary heart disease ranged from 4.7 to 37%, stroke from 3.5 to 19.6%, peripheral artery disease from 2.5 to 13.0%, and heart failure from 4.3 to 20.1%. In-hospital CVD mortality rates ranged from 5.6 to 10.8%. Direct costs due to CVD in hospitalized patients with T2DM were increased (> 50%) compared with patients without CVD. No studies analysed indirect costs of CVD in patients with T2DM.Conclusions
The burden of CVD among patients with T2DM, combined with the elevated costs of care, highlights the importance of early prevention as part of integrated management of the disease to improve clinical and economic outcomes.
Type 2 diabetes mellitus (T2DM) is a multifactorial, chronic, progressive disease, affecting more than 422 million people over the world, and having a significant societal and economic impact. Cardiovascular disease is the leading cause of morbidity and mortality in T2DM patients, who have higher rates of mortality than the non-diabetic population. T2DM is defined by its metabolic -mainly glucose-related- manifestations which serve as markers for controlling the evolution of disease. However, while the effect of control serum glucose levels on microvascular complications is acknowledged, its impact on macrovascular complications remains uncertain. Since 2008, new blood glucose-lowering agents have to demonstrate cardiovascular safety, and some have shown to reduce cardiovascular outcomes and mortality. However, the populations included in these large cardiovascular outcome trials differ from the general population, making results no fully generalisable. While randomised controlled trials are the gold standard for generating scientific evidence, observational studies conducted with secondary data of Electronic medical records (EMRs) are increasingly used as a source of complementary or confirmatory evidence, especially when RCTs are not feasible or unavailable. This work report an observational, population-based cohort study conducted in SIDIAP, a large Catalan general practitioners database that contains health data of 5,5 million people. We assessed cardiovascular outcomes and mortality in general, unselected T2DM population treated with non-insulin blood-glucose-lowering agents. The results are expected to be useful both for clinical and public health decision-making.
Background and objective
Dyslipidemia is one of the main risk factors in cardiovascular disease in patients with diabetes mellitus type 2 (DM2). The aim of this study is to evaluate the prevalence and risk factors associated with dyslipidemia in the population with diabetes mellitus type 2 in the region of Cantabria.
Material and methods
This is a transversal study carried out at Cantabrian primary health care centers (n = 680). A representative, random sample of the population with DM2, ranging from 18 to 85, was selected using a multistage procedure. The medical records were obtained, and by means of interviews the data of the risk factors to be studied was secured. The correlation with dyslipidemia was analyzed by means of logistic regression.
Results
There were 52.1% of males, the average age was 69.8, the evolution of diabetes was 9.99 years, 84.3% had arterial hypertension, 76.6% were overweight or obese and the average HbA1c was 6.96%. The prevalence of dyslipidemia was 85.3%, and in the bivariate analysis this is associated with a history of peripheral artery disease, controlled diabetes, antihypertensive treatment, glomerular filtration, HbA1c >7%, body fat estimated as being either overweight or obese, a history of cardiovascular disease, age and HbA1c.
In the multivariate analysis the independent factors were being female and a history of cardiovascular disease.
Conclusion
The prevalence of dyslipidemia in our study was 85.3%, and is consistent with figures found in previous published studies. The independent associated risk factors were being female and a past medical history of cardiovascular disease.
Objective:
The aim of this study was to determine the magnitude of cardiovascular disease risk factors among adult diabetic patients at Hiwot Fana Specialized University Hospital and Jugal Hospital, eastern Ethiopia.
Methods:
An institutional based cross sectional study was conducted on a total of 416 study participants (age ≥18 years) from February to March 2017. Data were collected using: structured questionnaires, measurements of weight, height, and blood pressure, and laboratory examination of blood lipids (total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein cholesterol) and fasting blood glucose. Data were analyzed using SPSS version 16.0 software packages. The association of cardiovascular disease risk factors with diabetes type, age, and sex was assessed by chi-square test.
Result:
The mean age of study participants was 52 years and 44% were male. Dyslipidemia (90.6%), physical inactivity (76%), and hypertension (62.7%) were the most common cardiovascular disease risks factors identified among diabetic patients. It was also observed that 68.5% of the study participants had uncontrolled blood glucose level. Hypertension was significant in patients over 65 compared to those ≤65 years of age (p < 0.023). Females were considered to be significantly physically inactive compared to males (p < 0.001).
Conclusion:
Dyslipidemia is the most common risk factor of CVD in individuals with Types 1 and 2 diabetes mellitus. Identification and treatment of lipid abnormalities is very important. Controlling hypertension among older patients and lifestyle modification among female diabetic patients are also recommended.
Resumen
Antecedentes y objetivo
La dislipidemia es uno de los principales factores de riesgo de enfermedad cardiovascular en pacientes con diabetes mellitus tipo 2 (DM2). El objetivo de este estudio es evaluar la prevalencia y factores de riesgo asociados a la dislipidemia en la población con DM2 de la Comunidad de Cantabria.
Material y métodos
Es un estudio transversal realizado en centros de Atención Primaria del Servicio Cántabro de Salud (n = 680). Se seleccionó una muestra aleatorizada representativa de la población con DM2 de 18 a 85 años mediante un procedimiento polietápico. Se obtuvieron de la historia clínica y mediante entrevista los datos de los factores de riesgo a estudio. Se analizó la asociación con la dislipidemia mediante regresión logística.
Resultados
El 52,1% eran hombres, la edad media fue de 69,8 años, la evolución de la diabetes de 9,99 años, el 84,3% tenían HTA, el 76,6% sobrepeso/obesidad y la HbA1c media era de 6,96%. La prevalencia de dislipidemia fue del 85,3% y en el análisis bivariado se asoció con antecedente de enfermedad vascular periférica, diabetes controlada, tratamiento antihipertensivo, filtrado glomerular, HbA1c > 7%, grasa corporal estimada en sobrepeso y obesidad, antecedente de enfermedad cardiovascular, edad y HbA1c.
En el análisis multivariante los factores independientes fueron el sexo femenino y el antecedente de enfermedad cardiovascular.
Conclusiones
La prevalencia de dislipidemia en nuestro estudio fue del 85,3% y es consistente con la encontrada en estudios previos publicados. Los factores de riesgo asociados de forma independiente fueron el sexo femenino y el antecedente personal de enfermedad cardiovascular.
Obesity must be considered a real pathology. In the world wide, obesity represent one of the major public health issue associated with increased morbidity and mortality. Overweight or obesity, in fact, significantly increases the risk of contracting diseases, such as: arterial hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, cerebral vasculopathy, gallbladder lithiasis, arthropathy, ovarian polycytosis, sleep apnea syndrome, and some neoplasms. Despite numerous informative campaigns, unfortunately, the fight against obesity does not seem to work: in the last years, the prevalence continued to increase. The progressive and rapid increase in the incidence of obesity, which has characterized most of the economically advanced countries in the last decade, has been the main stimulus for the research of the mechanisms underlying this pathology and the related disorders. The aims of this review is to provide a revision of the literature in order to define obesity as diseases, secondly to highlight the limits and the inaccuracy of common tools used for the diagnosis of obesity, and as a third thing to strengthen the concept of the complexity of obesity as a disease among political health care providers. Obesity may be viewed as a multifactorial pathology and chronic low-grade inflammatory disease. In fact, people affected by obesity have greater risk of developing comorbility and morbility, respect to healthy. Hence, the absolute therapeutic benefit is directly proportional to the basic risk. So, internationally interest on early diagnosis of obesity is growing to avoid under- and overdiagnosis consequences. Therefore, the consequences are an aggravation of the disease and an increase in obesity related pathology like diabetes, cardiovascular disease, and cancer. The most widely used parameter for diagnosis, body mass index (BMI) is not suitable for assessing the body fat. In fact, several studies demonstrate that BMI alone cannot define obesity, which consists not so much in weight gain as in excess fat mass. The use of suitable tools for the assessment of fat mass percentage combined with clinical and genetic analysis allowed to identify different phenotypes of obesity, which explain the various paradoxes of obesity. It is essential to adopt all possible strategies to be able to combat obesity, ameliorate the suffering of patients, and reduce the social and treatment costs of obesity.
Background:
Cardiovascular disease (CVD) is a common comorbidity in type 2 diabetes (T2DM). CVD's prevalence has been growing over time.
Purpose:
To estimate the current prevalence of CVD among adults with T2DM by reviewing literature published within the last 10 years (2007-March 2017).
Methods:
We searched Medline, Embase, and proceedings of major scientific meetings for original research documenting the prevalence of CVD in T2DM. CVD included stroke, myocardial infarction, angina pectoris, heart failure, ischemic heart disease, cardiovascular disease, coronary heart disease, atherosclerosis, and cardiovascular death. No restrictions were placed on country of origin or publication language. Two reviewers independently searched for articles and extracted data, adjudicating results through consensus. Data were summarized descriptively. Risk of bias was examined by applying the STROBE checklist.
Results:
We analyzed data from 57 articles with 4,549,481 persons having T2DM. Europe produced the most articles (46%), followed by the Western Pacific/China (21%), and North America (13%). Overall in 4,549,481 persons with T2DM, 52.0% were male, 47.0% were obese, aged 63.6 ± 6.9 years old, with T2DM duration of 10.4 ± 3.7 years. CVD affected 32.2% overall (53 studies, N = 4,289,140); 29.1% had atherosclerosis (4 studies, N = 1153), 21.2% had coronary heart disease (42 articles, N = 3,833,200), 14.9% heart failure (14 studies, N = 601,154), 14.6% angina (4 studies, N = 354,743), 10.0% myocardial infarction (13 studies, N = 3,518,833) and 7.6% stroke (39 studies, N = 3,901,505). CVD was the cause of death in 9.9% of T2DM patients (representing 50.3% of all deaths). Risk of bias was low; 80 ± 12% of STROBE checklist items were adequately addressed.
Conclusions:
Globally, overall CVD affects approximately 32.2% of all persons with T2DM. CVD is a major cause of mortality among people with T2DM, accounting for approximately half of all deaths over the study period. Coronary artery disease and stroke were the major contributors.
Background
Treatment of patients with type 2 diabetes mellitus (T2DM) and a history of cardiovascular (CV) disease or CV risk factors may present clinical challenges due to the presence of comorbid conditions and the use of concomitant medications. The sodium glucose co-transporter 2 inhibitor, canagliflozin, has been shown to improve glycaemic control and reduce body weight and blood pressure (BP) with a favourable tolerability profile in a broad range of patients with T2DM. This post hoc analysis assessed the efficacy and safety of canagliflozin in patients with T2DM based on CV disease history or CV risk factors. Methods
Analyses were based on pooled data from four 26-week, placebo-controlled, Phase 3 studies that evaluated canagliflozin 100 and 300 mg in patients with T2DM (N = 2313; mean HbA1c, 8.0%; body weight, 89 kg; systolic BP, 128 mmHg). Changes from baseline to week 26 in HbA1c, body weight, and systolic BP were assessed based on history of CV disease, history of hypertension, baseline statin use, and number of CV risk factors. Safety was assessed based on adverse event (AE) reports. ResultsAt week 26, both canagliflozin doses lowered HbA1c, body weight, and systolic BP compared with placebo in patients with and without CV disease history or risk factors. Placebo-subtracted HbA1c reductions with canagliflozin 100 and 300 mg were similar in patients with a history of CV disease (−0.95 and −1.07%) versus no history of CV disease (−0.71 and −0.90%), history of hypertension (−0.72 and −0.89%) versus no history of hypertension (−0.73 and −0.95%), baseline statin use (−0.77 and −0.99%) versus no statin use (−0.69 and −0.85%), and 0–1 CV risk factor (−0.72 and −0.87%) versus ≥2 CV risk factors (−0.74 and −1.02%). Similar body weight and systolic BP reductions were seen with canagliflozin versus placebo across subgroups. The incidence of AEs, AEs leading to discontinuation, and serious AEs was similar across subgroups. Conclusions
The efficacy and safety of canagliflozin were generally consistent across subgroups of patients with T2DM and varying degrees of CV disease history or risk factors.Trial registration numbers and dates ClinicalTrials.gov: NCT01081834, 4 March 2010; NCT01106625, 1 April 2010; NCT01106677, 1 April 2010; NCT01106690, 1 April 2010
Background/aim:
Diabetes mellitus is a risk factor for cardiovascular diseases (CVDs), which are among the major causes of deaths in type 2 diabetes (T2D). The purpose of the present study was to determine the association of C282Y and H63D mutations in the HFE gene with increased risk of coronary artery disease (CAD) in T2D patients.
Materials and methods:
Two hundred and ninety individuals were divided into two groups: a case group and a control group. Genomic DNA of peripheral venous blood cells was extracted and the HFE gene mutations were analyzed using the PCR-RFLP technique.
Results:
Data analysis revealed a significant difference between the allele frequencies of H63D and C282Y mutations between the case group and the controls (P < 0.05). The relationships between the GA and GG genotypes in C282Y and H63D mutations in terms of fasting blood sugar (FBS), lipid profile (total cholesterol, triglycerides, high-density lipoproteins (HDL), low-density lipoproteins), body mass index (BMI), HbA1c, micro albuminuria, and creatine levels did not show a significant differences between the two groups (P > 0.05). Using a logistic regression model, BMI, FBS, HDL, and total cholesterol levels were significantly different with independent predictors of CVD (P < 0.05).
Conclusion:
Our results revealed a significant correlation between C282Y and H63D mutations and the development of CAD in T2D patients.
Introduction: Cardiovascular disease (CVD) with its high prevalence is mainly responsible for the high mortality and morbidity in type 2 diabetic patients. The aim of this study was to determine the prevalence of cardiovascular risk factors in patients with type 2 diabetes. Materials and Methods: Clinical information for 752 type 2 diabetic patients was collected in a cross sectional survey. History and physical examination were recorded. Laboratory tests were done for all patients. Results: Data for a total of 752 patients (355 males and 397 females) of type 2 diabetes were analyzed. The mean age of patients was 52.7±10.5 years and the mean duration of first time diagnosis of diabetes was 7.9 ±6.4 years, 51.6% of patients had hypertension. The prevalences of overweight and obesity were 52.5% and 25.7% respectively. Lipid abnormalities were prevalent in a large numbers of our patients, 95.2% had total cholesterol > 200 mg/dL, 3.1% of patients had triglycerides > 150 mg/dl. The prevalences of low HDL-c and dense LDL were 86.9% and 65.8% respectively; 73.5% of our patients had metabolic syndrome. HbA1C>7% was found in 75% of patients. Renal involvement was observed in our patients; 21.5% of patients had microalbuminuria, 1.6% macroalbuminuria and 8.8% had chronic kidney disease. Conclusion: The high prevalence of CVD in our type 2 diabetic patients found demonstrate the need for more improvement in prevention and treatment of such patients.
Dyslipidemia is one of the major risk factors for Cardiovascular Disease (CVD) that coexists with diabetes. It plays an important role in the development and progress of atherosclerosis, the underlying pathogenesis of CVD. Hyperglycemia is associated with adverse lipid profiles. An atherogenic lipid profile, consisting of high Triglycerides (TG) and small dense Low-Density Lipoprotein Cholesterol (LDL-C) and low High-Density Lipoprotein Cholesterol (HDL-C), is common not only in patients with overt diabetes but also in individuals with prediabetes. The impact of dyslipidemia on risk of CVD in patients with hyperglycemia has been extensively studied. Reduced HDL-C is well documented as an independent predictor of CVD events, the role of TG as an independent risk factor for CVD is, however, controversial. Recently, the interest to use novel parameters such as total cholesterol (TC) to HDL ratio (TC/HDL-C), non- HDL-cholesterol (non-HDL-C), apolipoprotein B (apoB) and apolipoprotein A (apoA) to assess CVD risk has increased. This chapter provides a comprehensive review of the physiology, pathophysiology, prognosis and management of dyslipidemia in individuals with different glycemic levels. The ethnic differences in occurrence of dyslipidemia are also addressed.
Background and purpose: Ischemic Heart Disease (IHD) is one of the most important complications of diabetes mellitus (DM). This study was designed to investigate the prevalence of IHD and related factors in patients with type II DM in north of Iran. Materials and methods: A cross sectional study was conducted in 1021 patients with diabetes type II attending endocrine clinics affiliated with Mazandaran University of Medical Sciences, Iran, 2010 to 2012. Age, gender, history of myocardial infarction, hypertension, hyperlipidemia, smoking and other recognized complications of DM were recorded. All patients were referred to cardiologist and the exercise test was used and if needed the thallium perfusion scan and coronary angiography were done for patients without history of myocardial infarction, coronary artery bypass surgery or stent placement. Results: There were 1021 patients and 907 were female (88.8%). Mean age and duration of diabetes were 54.4 (95% CI: 53.8- 55.1) and 8.8 (95% CI: 8.4 - 9.2) years, respectively. Almost 87% (95% CI: 85-89) and 53% (95% CI: 50-56) had dyslipidemia and hypertension, respectively. Among the patients, 274 patients (37% males and 25% females, 26.8%; 95% CI: 24.1-29.5) were suffering from IHD (P =0.006). According to regression logistic analysis duration of diabetes, older age, hypertension, and low left ventricular ejection fraction were independent predictor factors for IHD. Conclusion: Approximately one-third of diabetic patients are suffering from IHD. This disorder can be asymptomatic in individuals with diabetes, therefore, it may not be diagnosed in almost half of patients. Most important associated factors are older age, duration of diabetes, hypertension and low left ventricular ejection fraction. © 2015, Mazandaran University of Medical Sciences. All rights reserved.
Previous studies have clearly shown that epicardial adipose tissue (EAT) mass is associated with increased incidence of coronary artery disease. In the present study, the relationship between the EAT volume measured by cardiac multislice computerized tomography (MSCT) and cardiovascular risk was investigated in patients with type 2 diabetes mellitus. Ninety type 2 diabetic patients and 62 healthy controls were included in the study. We examined metabolic and anthropometric parameters including body mass index (BMI), fasting glucose and serum lipids and EAT volume of patients in comparison to those of control subjects. EAT volume was higher in Type 2 diabetic patients compared to control group (172.75 ± 64.85 cm3 and 68.94 ± 37.74 cm3, respectively) (p<0.001). Type 2 diabetic patients had significantly higher levels of fasting glucose (p=0.014), total cholesterol (p<0.001), triglycerides (p=0,017) and LDL-cholesterol (p=0,022) versus control group. EAT volume was correlated with BMI, glucose, HbA1c, LDL-cholesterol, total cholesterol. In a stepwise regression analysis, Hba1c emerged as a significant predictor of EAT volume (ß= 0.610, p0.001), accounting for 18% of its variability. These results provide additional evidence for the presence of subclinical cardiovascular disease (CVD) in type 2 diabetic patients. It is also important to note that our findings reveal significant relationships between HBA1c and cardiovascular changes and underline the importance of glucose control in predicting CVD.
The aim of this study was to evaluate the morphological nasal changes associated with rapid maxillary expansion (RME) which is used in the treatment of skeletal maxillary narrowness. The study was performed with 20 patients 12 girls and 8 boys between the ages of 10 and 15 (13.4±0.99) and compared with a control group consisting of 16 subjects 10 girls and 6 boys between the ages of 10 and 15 (13.25±1.18). Lateral and anteroposterior radiographs were taken before RME (T1), after RME (T2) , and after retention (T3) . Greater alar cartilage width, nasal cavity width, vertical and sagittal movement of the tip of nose, SNA° and nasolabial angle measurements were evaluated to understand the morphological and positional changes of the nose associated with RME. The results showed that the greater alar cartilage width returned to its original position, the nasal cavity width increased, and the tip of the nose moved downward and minimally forward; as well, SNA° returned to its original value and a small increase occurred in the nasolabial angle due to RME. Soft tissue changes may be considered clinically non-significant compared with the controls. RME did not affect the patients’ frontal nasal appearance and mid-face soft tissue profile.
Aims:
To evaluate current evidence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood pressure, heart rate, and hypertension in patients with type 2 diabetes.
Methods:
Medline, Embase, the Cochrane library, and the website www.clinicaltrials.gov were searched on April 5th, 2014. Randomized-controlled trials with available data were included if they compared GLP-1RAs with placebo and traditional antidiabetic drugs in patients with type 2 diabetes with duration ≥ 12 weeks. Weighted mean difference for blood pressure and heart rate, odds ratio (OR) for hypertension were calculated by random-effect model. Network meta-analysis was performed to supplement direct comparisons.
Results:
Sixty trials with 14 treatments were included. Compared with placebo, insulin, and sulfonylureas, GLP-1RAs decreased systolic blood pressure with range from -1.84mmHg (95% CI: -3.48 to -0.20) to -4.60mmHg (95% CI: -7.18 to -2.03). Compared with placebo, a reduction in diastolic blood pressure was detected significantly only for exenatide-10μg-twice-daily (-1.08mmHg, 95% CI: -1.78 to -0.33). Exenatide (2mg once weekly), liraglutide 1.2mg once daily), and liraglutide (1.8mg once daily) increased heart rate by 3.35 (95% CI: 1.23-5.50), 2.06 (95% CI: 0.43, 3.74), and 2.35 (95% CI: 0.94-3.76) beats/min versus placebo. This effect was evident compared with active control (range: 2.22-3.62). No significant association between incident hypertension and GLP-1RAs was detected, except for the association between exenatide-10μg-twice-daily and sulfonylureas (OR, 0.40, 95% CI: 0.16, 0.82).
Conclusions:
GLP-1RAs were associated with modest reduction on blood pressure, a slight increase in heart rate, yet no significant association with hypertension. Further investigation to explore mechanisms is warranted.
Macrovascular and microvascular complications that accompany Type 2 diabetes mellitus (T2DM) add to the burden among patients. The purpose of this systematic review is to conduct a comprehensive search of the medical literature investigating the prevalence of cardiovascular (CV) complications and assess their impact on healthcare costs, quality of life and mortality among patients with T2DM in the context of microvascular complications. A total of 76 studies and reports were used in this systematic review. Hypertension was the most prevalent complication among patients with T2DM. The additional cost burden due to CV complications was higher than any other complication except end-stage renal disease. Quality of life was much lower among patients with CV complications and T2DM, and mortality was higher than either illness alone.
To evaluate thoracic periaortic adipose tissue (TAT) volume in patients with subclinical hypothyroidism (SH) in comparison with controls and in relation to cardiovascular risk factors.
The study population consisted of 28 newly diagnosed SH patients (mean (s.d.) age: 37.3 (±11.4) years, 85.7% were females) and 37 healthy volunteers (mean (s.d.) age: 35.3 (±10.7) years, 81.5% were females). Comparisons between patient and control groups used demographic characteristics, anthropometrics, and laboratory findings. All participants underwent thoracic radiographic assessment in the supine position, using an eight-slice multidetector computed tomography scanner and TAT volume was measured.
The TAT volume was determined to be 27.2 (±12.7) cm(3) in the SH group and 16.3 (±8.1) cm(3) in the control group, and the difference was statistically significant (P<0.001). In addition, TSH levels were significantly higher in the patient group compared with the control group (P<0.001). A significant correlation was also found between TSH levels and TAT volume (r=0.572; P<0.001). In SH patients, no significant difference was noted in TAT levels with respect to sex (P=0.383) or concomitant smoking status (P=0.426).
Our findings indicate that SH patients have significantly higher TAT values than controls and that increased TAT levels correlate with increased TSH levels.
© 2015 European Society of Endocrinology.
The purpose of this study was to assess risk of cardiovascular disease (CVD) by comparing the Framingham and United Kingdom Prospective Diabetes Study (UKPDS) risk equations in Korean adults with type 2 diabetes (T2DM) and metabolic syndrome.
The study was a cross-sectional survey enrolling a convenience sample of 110 Korean adults with T2DM and metabolic syndrome. The 10-year CVD risk scores were calculated using the Framingham risk equation and UKPDS risk engines.
Overall participants had a moderate prevalence (average, 64.3%) of metabolic syndrome factors, with the most prevalent being abdominal obesity (86.4%) and elevated blood pressure (78.2%). A lower percentage of women were current smokers and consumed alcohol than men, whereas a higher percentage of men had their weight and stress controlled than women. The mean scores of 10-year CVD risk using the Framingham and UKPDS equations were 14.55% and 15.99%, respectively. However, there were no significant differences between results of the 2 equations. Regarding level of CVD risk, the percentage of high risk (>20%) was about 24% using both equations. Also, the area under the receiver operating characteristic curves using Framingham and UKPDS equations was similar: 0.707 and 0.696, respectively, which indicated moderate accuracy.
About one-fourth of adults with T2DM and metabolic syndrome had high level of CVD risk (>20%). In practice, people with diabetes and metabolic syndrome could be managed earlier and more intensively based on their risk estimated by the Framingham or UKPDS equations.
© 2015 The Author(s).
The relationship between cardiovascular disease and diabetic peripheral neuropathy is mainly sustained by data retrieved from cross-sectional studies focused on cardiovascular risk factors. We aimed to assess the presence of cardiovascular disease as a risk factor for developing diabetic peripheral neuropathy in a type 2 diabetes mellitus population.
A 10-year prospective, primary care, multicentre study in a randomly selected cohort. Cardiovascular disease presence included stroke, coronary artery disease and/or peripheral ischaemia. Diabetic peripheral neuropathy diagnosis was based on clinical neurological examination as well as the neuropathy symptoms score and nerve conduction studies.
Three hundred and ten (N=310) patients were initially recruited. Two-hundred and sixty seven (N=267) patients were included in the study. Diabetic peripheral neuropathy cumulative incidence was 18.3% (95% confidence intervals 14.1-23.4; N=49). Diabetic peripheral neuropathy development was significantly more frequent in participants presenting with cardiovascular disease at baseline (P=0.01). In the final logistic regression analysis, the presence of cardiovascular disease remained associated with an increased risk for diabetic peripheral neuropathy (odds ratio 2.32, 95% confidence intervals 1.03-5.22) in addition to diabetes duration and low density lipoprotein-cholesterol levels.
In our series, type 2 diabetes mellitus patients with cardiovascular disease at baseline present with an increased risk of developing diabetic peripheral neuropathy at 10 years of follow-up. Our results suggest that measures aimed at the prevention, control and treatment of cardiovascular disease can also help prevent diabetic peripheral neuropathy development.
© The European Society of Cardiology 2014.
To test the effectiveness and safety of saxagliptin 5 mg/d in patients with type 2 diabetes mellitus (T2DM) with and without history of cardiovascular disease (CVD) or cardiovascular (CV) risk factors.
The authors conducted a post hoc analysis of data from 3 randomized studies that compared saxagliptin versus placebo as initial combination therapy with metformin for 24 weeks (N = 648) and versus placebo as an add-on to insulin with and without metformin for 24 weeks (N = 455), and assessed noninferiority to glipizide as an add-on to metformin for 52 weeks (N = 858). Efficacy outcomes were the adjusted mean change from baseline in glycated hemoglobin (HbA1c) level, fasting plasma glucose concentration, and body weight and the proportion of patients achieving an HbA1c level < 7%. Pairwise comparisons were performed in subgroups with 1) history/no history of CVD, 2) ≥ 2 versus 0 to 1 CV risk factors, 3) hypertension/no hypertension, and 4) statin use/no statin use. Adverse events (AE) and hypoglycemia were monitored.
In the initial combination therapy study, reductions in HbA1c level from baseline were greater with saxagliptin versus placebo in all subgroups (difference [saxagliptin - placebo], -0.38% to -0.67%). In the add-on to insulin ± metformin study, differences in adjusted mean change in HbA1c level versus placebo ranged from -0.23% to -0.58% across subgroups. In the noninferiority to glipizide study, adjusted mean changes in HbA1c level were comparable between saxagliptin and glipizide, across subgroups (difference, 0.08%-0.21%). No evidence suggested clinically relevant treatment-by-subgroup interactions in pairwise comparison. Incidences of ≥ 1 AE were comparable across subgroups. Incidences of confirmed hypoglycemia with saxagliptin were 0 in both metformin add-on studies and 1.2% to 7.8% with saxagliptin + insulin ± metformin.
In patients with T2DM, saxagliptin 5 mg/d was similarly effective in improving glycemic control, with an AE profile similar to that of placebo, irrespective of CVD history, number of CV risk factors, hypertension, or statin use.
www.ClinicalTrials.gov identifiers: NCT00327015, NCT00575588, NCT00757588.
Objective
To evaluate thoracic periaortic adipose tissue (TAT) burden in patients with type 2 diabetes mellitus (DM) in comparison with controls and in relation to cardiovascular risk factors.
Methods
A total of 93 patients with type 2 DM (mean (standard deviation; SD) age: 56.7 (11.2) years, 71.0 % were men) and 85 nondiabetic control subjects (mean (SD) age: 54.6 (10.9) years, 58.8 % were men) who were admitted to Mevlana University hospital between January 2011 and June 2013 and underwent multidetector computed tomography for any reason were included in this retrospective cohort study. Patient and control groups were compared in terms of demographic characteristics, anthropometrics, and laboratory findings. TAT volume was evaluated in both groups, while correlates of TAT were determined via linear regression analysis among patients.
Results
In patients with type 2 DM, TAT volume (40.1 (23.9) versus 16.9 (7.7) cm3, p
Objective:
To determine the risk of developing coronary heart disease (CHD) in a cross-sectional sample of Puerto Rico residents through an analysis of the 10-year Framingham risk score.
Methods:
An exploratory, retrospective, cross-sectional study of the medical records of patients 35 years or older who each visited the office of 1 of the 4 participating physicians on or after July 1, 2007.
Results:
Data for 453 patients were extracted from the medical records, but 96 cases were excluded because of incomplete data or the patients' not fulfilling the inclusion criteria, thus yielding a total sample of 357 patients. The average patient age was 58 years old (+/- 11.8); the majority (58%) was female. Eight of 10 patients were either overweight or obese. Eighty-five percent reported having at least 1 cardio-metabolic condition. Of these, 72.3% self-reported having hypertension; 38.4%, dyslipidemia; and 37.8%, diabetes. Many patients were not at goal for blood pressure or for lipid and glucose parameters nor were these patients taking any medication for these conditions. Nearly one-third of the participants had a 10% or greater 10-year risk of developing CHD. Compared with women, men were 3.3 times more likely to have a 10-year CHD risk of 10% or greater and 4.2 times more likely to have a risk of 20% or greater.
Conclusion:
A substantial number of patients had risk factors for developing CHD and were not at goal for specific parameters. Larger scale epidemiological studies should be conducted to assess CHD risk in Puerto Rico so that public health initiatives to reduce this risk might be proposed.
AimsTo evaluate the possible relationships between a health policy decision, in relation to the diabetes education strategies and the metabolic control outcomes.
Objective:
This post hoc analysis sought to assess the efficacy, safety, and tolerability of saxagliptin in patients with type 2 diabetes mellitus and cardiovascular (CV) risk factors or disease (CVD).
Methods:
Data from 5 randomized controlled trials were pooled to compare saxagliptin 5 mg with placebo: 2 studies of saxagliptin as monotherapy in drug-naïve patients and 1 each of saxagliptin as add-on therapy to metformin, glyburide, or a thiazolidinedione. Analysis was performed according to the following baseline/trial entry criteria: 1) history/no history of CVD; 2) ≥ 2 versus 0 to 1 CV risk factors; 3) statin use versus no statin use; and 4) hypertension versus no hypertension. Change from baseline glycated hemoglobin (HbA1c), fasting plasma glucose, and postprandial glucose levels; and the proportion of patients achieving an HbA1c level < 7% were analyzed (week 24). Safety was assessed by adverse events, hypoglycemia, and body weight.
Results:
In total, 882 patients received saxagliptin 5 mg and 799 received placebo. Differences in adjusted mean change from baseline HbA1c (95% CI) were greater with saxagliptin compared with placebo in patients with a history of CVD (-0.64% [-0.90 to -0.38]) and no history of CVD (-0.68% [-0.78 to -0.58]); with ≥ 2 CV risk factors (-0.73% [-0.85 to -0.60]) and 0 to 1 CV risk factor (-0.62% [-0.75 to -0.48]); with statin use (-0.70% [-0.89 to -0.52]) and no statin use (-0.66% [-0.77 to -0.56]); and with hypertension (-0.69% [-0.82 to -0.57]) and no hypertension (-0.66% [-0.80 to -0.52]). Saxagliptin was well tolerated, with similar adverse event rates and types compared with placebo. There was a < 1% rate of confirmed hypoglycemia in all groups except in patients with CV history who received placebo (2.1%).
Conclusion:
Saxagliptin improved glycemic measures, resulted in low rates of confirmed hypoglycemia, and was well tolerated in patients with or without CVD and CV risk factors.
Aims:
Aside from lowering blood glucose, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) attract much attention because of their cardioprotective effects. The aim of this study was to assess the blood pressure-lowering effects of the GLP-1 RAs exenatide and liraglutide compared with other common drugs used to treat type 2 diabetes (T2DM) based on randomized controlled trials (RCTs) including data describing complete blood pressure (BP) changes from baseline.
Methods:
We searched the major databases for published or unpublished RCTs that had been performed in patients with T2DM and compared the effects of exenatide and liraglutide to those of other common drugs used to treat T2DM. The RCTs that included data describing BP changes between the baseline and the end of the study were selected for further analysis.
Results:
A total of 16 RCTs that enrolled 3443 patients in the GLP-1 RA treatment group and 2417 subjects in the control group were included in this meta-analysis. The GLP-1 RA exenatide reduced systolic blood pressure (SBP) when compared with both placebo and insulin glargine, with mean differences of -5.24 and -3.46 mmHg, respectively, and with 95% confidence intervals (CI) of -6.88 to -3.59, p < 0.00001 and -3.63 to -3.29, p < 0.00001, respectively. Meanwhile, in the exenatide-treated group, diastolic blood pressure (DBP) was reduced by -5.91 mmHg, with a 95% CI of -7.53 to -4.28, p < 0.00001 compared with the placebo group, and -0.99 mmHg with a 95% CI of -1.12 to -0.87, p < 0.00001 compared with the sitagliptin group. SBP changes in this meta-analysis were assessed in the groups treated with 1.2 or 1.8 mg liraglutide per day. In the 1.2 mg-treated group, liraglutide treatment reduced SBP compared with placebo and glimepiride treatment, with mean differences of -5.60 and -2.38 mmHg, and 95% CIs of -5.84 to -5.36, p < 0.00001 and -4.75 to -0.01, p = 0.05, respectively. In the 1.8-mg-treated group, liraglutide also reduced SBP compared with placebo and glimepiride treatment with mean differences of -4.49 and -2.62 mmHg, and a 95% CI of -4.73 to -4.26, p < 0.00001, and -2.91 to -2.33, p < 0.00001, respectively.
Conclusion:
Treatment with the GLP-1 RAs exenatide and liraglutide reduced SBP and DBP by 1 to 5 mmHg compared with some other anti-diabetic drugs including insulin, glimepiride and placebo for patients with T2DM. GLP-1 RAs may offer an alternative therapy for these patients and will help provide extra cardiovascular benefits.
Background: Weight management is considered a key therapeutic strategy in type 2 diabetes mellitus. However, little is known about the impact of weight loss or body mass index (BMI) reduction on type 2 diabetes-related healthcare costs.
Objective: The aim of this study was to estimate the economic impact of change in BMI among patients with type 2 diabetes mellitus from the Spanish healthcare system perspective.
Methods: The ECOBIM study is an observational, non-interventional study in which data on BMI change and costs incurred by patients with type 2 diabetes were collected cross-sectionally and retrospectively for a 12-month period. Generalized linear mixed models were applied to estimate the effects of (i) BMI change in general (one-slope model); (ii) BMI gain and no BMI gain (two-slope model); and (iii) BMI gain and no BMI gain among obese and non-obese patients (four-slope model).
Results: We studied 738 patients with a mean (SD) age of 66 (11) years and BMI of 30.6 (5.2) kg/m2. During the 12-month study period, 41.2% of patients gained BMI (BMI gainers) and 58.8% experienced either loss (52.2%) or no change (6.6%) in BMI (non-BMI gainers). One-unit gain (or loss) in BMI was significantly (p<0.001) associated with a 2.4% cost increase (or decrease) [one-slope model]. Every unit gain in BMI was associated with a 20.0% increase in costs among BMI gainers while losing one unit was associated with an 8.0% decrease in costs among non-BMI gainers (two-slope model, p<0.01). The economic benefit associated with reducing one BMI unit was 9.4% cost decrease in obese and 2.7% in non-obese patients (4-slope model).
Conclusion: An increase in BMI among patients with type 2 diabetes was associated with increased 1-year direct healthcare costs. A reduction in BMI was associated with appreciable short-term economic benefits, especially in obese patients.
Background: This study aimed to estimate the prevalence of cardiovascular disease (CVD) among patients attending The University Hospital of the West Indies diabetes clinic and to examine the relationship between prevalent CVD and its risk factors. Methods: We analyzed data from 174 patients selected from the University Hospital of the West Indies diabetes clinic using gender-stratified random sampling. An interviewer-administered questionnaire was used to obtain data on self-reported CVD (coronary heart disease [CHD], cerebrovascular disease, and peripheral vascular disease [PVD]), physical activity, alcohol consumption, and smoking. Trained nurses performed blood pressure and anthropometric measurements. A capillary blood sample was collected to measure glycosylated hemoglobin, and urine was tested for protein and microalbumin. Means and proportions for patient charac-teristics, CVD outcomes, and risk factors were calculated. Logistic regression was used to identify factors independently associated with CVD. Results: Data from 129 women and 45 men (mean age 55.7 ± 14.7 years) were analyzed. The prevalence of any self-reported CVD (CHD, cerebrovascular disease, or PVD) was 34.5% (95% confidence interval [CI] 27.4–41.6). PVD had the highest prevalence (25.9%), compared with CHD (6.9%) and cerebrovascular disease (16.1%). There were no gender differences in the prevalence of CVD. Prevalence of CVD was higher among people $50 years, and those with high blood pressure, central obesity, high total cholesterol, and duration of diabetes $20 years. In multivariable models, duration of diabetes was the most consistent factor associated with CVD, odds ratio 1.41 (95% CI 1.15–1.73, P = 0.001) per five-year increment. Having blood pressure at the goal of ,130/80 mmHg and at least three physical activity sessions/ week were associated with lower odds of CVD, odds ratios 0.42 (95% CI 0.20–0.87, P = 0.020) and 0.37 (95% CI 0.16–0.82, P = 0.014), respectively. Conclusion: In this Jamaican setting, 35% of patients with diabetes have at least one CVD. Odds of CVD increased with diabetes duration, while good blood pressure control and increased physical activity were ameliorating factors.
Glucagon-like peptide 1 (GLP-1) is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally, as opposed to intravenously, and it retains its insulinotropic activity in patients with type 2 diabetes mellitus. GLP-1-based therapies, such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase 4, an enzyme that degrades endogenous GLP-1, have established effectiveness in lowering glucose levels and are routinely used to treat patients with type 2 diabetes. These agents regulate glucose metabolism through multiple mechanisms and have several effects on cardiovascular parameters. These effects, possibly independent of the glucose-lowering activity, include changes in blood pressure, endothelial function, body weight, cardiac metabolism, lipid metabolism, left ventricular function, atherosclerosis, and the response to ischemia-reperfusion injury. Thus, GLP-1-based therapies could potentially target both diabetes and cardiovascular disease. This Review highlights the mechanisms targeted by GLP-1-based therapies, and emphasizes current developments in incretin research that are relevant to cardiovascular risk and disease, as well as treatment with GLP-1 receptor agonists.
Obesity is a multifactorial disease resulting from interactions between susceptibility genes, psychosocial, and environmental factors. However, it is becoming evident that interindividual differences in obesity susceptibility depend also on epigenetic factors, although the mechanisms have not been fully elucidated. We have undertaken a genome-wide analysis of DNA methylation of human preadipocytes and mature adipocytes to examine the differences in methylation between them. We found hypomethylation occurring in 2,701 genes and hypermethylation in 1,070 genes after differentiation. Meanwhile, Gene Ontology analysis and Ingenuity Pathway Analysis showed many significant gene functions and pathways with altered methylation status after adipocyte differentiation. In addition, Signal-Net analysis showed that tumor necrosis factor-α, mitogen-activated protein kinase, and interleukin-8 were important to the formation of this network. Our results suggest that DNA methylation mechanisms may be involved in regulating the differentiation process of human preadipocytes.
The aim of this study in 2006-08 was to determine the prevalence and risk factors of CVD in an Iranian population of patients with type 2 diabetes mellitus. History and physical examinations were recorded and laboratory tests were performed in 752 patients attending the Mashhad Endocrine and Metabolism Research Center. The prevalence of CVD was 20.1%. CVD was significantly associated with age, duration of diabetes, hypertension, diabetic retinopathy, metabolic syndrome, renal insufficiency, triglycerides, high-density lipoprotein (HDL) cholesterol, uric acid and triglycerides/HDL ratio. Using a logistic regression model, age, metabolic syndrome and HDL cholesterol were significant independent predictors of CVD. The high prevalence of CVD in Iranian patients with type 2 diabetes underscores the importance of better detection and treatment of metabolic risk factors of CVD in these patients.
Lobeglitazone, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist with partial PPAR-α affinity, was developed to treat type 2 diabetes mellitus.
This study's aim was to evaluate the tolerability and pharmacokinetic (PK) properties of lobeglitazone to satisfy regulatory requirements for marketing approval in Korea.
A block-randomized, double-blind, placebo-controlled, single- and multiple-dose study was conducted in healthy subjects. In the pilot study, 4 subjects were administered 0.5 mg, including 1 receiving a placebo. Then, the single-dose study was conducted with 1, 2, 4, and 8 mg doses (8 subjects in each group, including 2 receiving placebos), followed by the multiple-dose study with 1, 2, and 4 mg doses (once daily for 7 days; 8 subjects in each group, including 2 receiving placebos). Serial samples of blood and urine were collected and drug concentrations were determined by high turbulence liquid chromatography-LC/MS/MS. Tolerability assessments were performed throughout the study. Adverse events (AEs) were determined from general health-related questions and self-reports.
Thirty-six (mean [SD]; age, 23.6 [2.7] years; weight, 70.0 [6.9] kg) and 25 Korean male subjects (age, 23.5 [3.1] years; weight 69.4 [9.4] kg) were enrolled in the single- and multiple-dose studies, respectively. The data from subjects administered lobeglitazone who completed the study (27, single; 18, multiple) was included in the PK analyses. In the single-dose study, the AUC and C(max) of lobeglitazone increased with the dose. After repeated dosing for 7 days, the accumulation ratio ranged from 1.1 to 1.4. A total of 25 AEs were reported by 11 (30.6%) and 8 subjects (33.3%) in the single- and multiple-dose studies, respectively. All AEs were mild in intensity and not serious.
Lobeglitazone was well tolerated in this small, selected group of healthy male Korean volunteers. The AUC and C(max) of lobeglitazone increased in a dose-proportional manner from 1 to 4 mg.
Type 2 diabetes mellitus (DM) and metabolic syndrome are associated with high risk of cardiovascular disease (CVD) and depression. Although lifestyle modifications including regular exercise and weight control are recommended as a primary approach to glycemic control and CVD risk reduction for people with DM and/or metabolic syndrome, little is known concerning the effects of CVD risk reduction interventions using psychobehavioral strategies in this population.
This pilot study investigated the effects of a 16-week CVD risk reduction intervention in Korean adults with type 2 DM and metabolic syndrome.
A prospective, pretest and posttest, controlled, quasi-experimental design enrolled a convenience sample of 43 Korean adults with type 2 DM and metabolic syndrome at a university hospital. The adults in the intervention group participated in a 16-week CVD risk reduction intervention consisting of 150 minutes of regular exercise per week; 200- to 300-kcal reduced daily diet for weight control; one-on-one psychobehavioral counseling based on constructs from the Transtheoretical Model such as processes of change, self-efficacy, and decisional balance; and telephone coaching for behavioral modification. Participants in the control group received a booklet with basic diabetic education as part of their routine care. Repeated-measures analysis of variance was used for analyzing the effects of the CVD risk reduction intervention on cardiometabolic risk factors including the UK Prospective Diabetes Study score for 10-year CVD risk, glycated hemoglobin (HbA1c), and depression.
The intervention group showed significant reductions (P < .05) at 16 weeks, compared with the control group on the UK Prospective Diabetes Study fatal risk scale (-1.73% vs -0.04%), triglycerides (-38.5 vs -15.1 mg/dL), fasting plasma glucose (-29.24 vs +1.77 mg/dL), HbA1c (-0.37% vs +0.17%), and depression (score, -3.24 vs 1.40) measurements.
This pilot study yielded evidence for the beneficial impact of the CVD risk reduction intervention for Korean adults with type 2 DM and metabolic syndrome on improved glycemic control, reduced CVD risk, and depression.
The majority of patients with type 2 diabetes mellitus have blood pressure (BP) exceeding the recommended value of <130/80 mm Hg. Optimal control of hyperglycemia and hypertension has been shown to reduce the incidence of macrovascular and microvascular complications due to diabetes. Treatment with the GLP-1 receptor agonist exenatide, previously demonstrated to reduce hemoglobin A(1C) and weight in subjects with type 2 diabetes, was associated with BP reduction in several studies.
This analysis explored the effects of exenatide vs. placebo or insulin on BP measurements in pooled data from six trials including 2,171 subjects studied for at least 6 months.
Overall, 6 months of exenatide treatment was associated with a significantly greater reduction in systolic BP (SBP) compared with placebo (least squares mean (s.e.): difference of -2.8 mm Hg (0.75); P = 0.0002) or insulin (difference of -3.7 mm Hg (0.85); P < 0.0001). No significant intergroup differences in diastolic BP (DBP) were observed. The majority of the intergroup difference was observed in subjects with SBP > or = 130 mm Hg (difference of -3.8 mm Hg (1.08) from placebo: P = 0.0004; difference of -4.0 mm Hg (1.01) from insulin; P < 0.0001). The largest intertreatment differences between exenatide and comparators were observed in subjects with SBP >/=150 mm Hg. Similar responses were observed in African-American subjects. A weak correlation between the amount of weight lost and reduction in SBP was found (r = 0.09, P = 0.002) for exenatide-treated subjects.
These results support the need for a prospective, randomized, controlled study of BP changes during exenatide treatment in patients with hypertension and type 2 diabetes.
The differences of the clinical characteristics, risk factors, treatment and prognosis in coronary heart disease (CHD) patients from different races, area and countries are rarely reported.
Collecting, comparing and analyzing the clinical data and blood examination results of 650 Chinese Han and 640 German Caucasian patients with CHD.
The ratio of the first hospitalization because of CHD in Chinese patients was higher than that in Germans (95.1 vs. 38.1% P < 0.01). CHD occurred most frequently in elder men of both nations. The German CHD patients combined with hypertension, dyslipidemia and abnormal glucose metabolism were clearly more often than Chinese patients. Other risk factors such as fibrinogen, homocysteine and the proportion of positive family history of premature CHD, obesity, hyperuricemia were higher in German patients than that in Chinese patients. However, the ratio of smoking, acute myocardial infarction and the levels of high-sensitivity C-reactive protein in Chinese patients were obviously higher than that in Germans (P < 0.01, P < 0.05). The use of aspirin in both groups was the same, but the use of statins, beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers were distinctly lower in Chinese patients compared to Germans (P < 0.01, P < 0.05). The proportion of percutaneous coronary intervention and coronary artery bypass grafting in Chinese patients was lower than that in Germans (P < 0.01). The usage of drug-eluting stents to bare-metal stents was slightly higher in German patients, whereas it was obviously higher in Chinese patients (P < 0.01).
There were significant differences in clinical characteristics, risk factors and treatment of Chinese Han and German Caucasian patients with CHD.
Background Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial. Methods 3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or. glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. in the conventional group, the aim was the best achievable FPG with diet atone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye,or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy. Findings Over 10 years, haemoglobin A(1c) (HbA(1c)) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group-an 11% reduction. There was no difference in HbA(1c) among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg). Interpretation Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes. None of the individual drugs had an adverse effect on cardiovascular outcomes. All intensive treatment increased the risk of hypoglycaemia.
Context
Microalbuminuria is a risk factor for cardiovascular (CV) events. The
relationship between the degree of albuminuria and CV risk is unclear.Objectives
To estimate the risk of CV events in high-risk individuals with diabetes
mellitus (DM) and without DM who have microalbuminuria and to determine whether
levels of albuminuria below the microalbuminuria threshold increase CV risk.Design
The Heart Outcomes Prevention Evaluation study, a cohort study conducted
between 1994 and 1999 with a median 4.5 years of follow-up.Setting
Community and academic practices in North and South America and Europe.Participants
Individuals aged 55 years or more with a history of CV disease (n =
5545) or DM and at least 1 CV risk factor (n = 3498) and a baseline urine
albumin/creatinine ratio (ACR) measurement.Main Outcome Measures
Cardiovascular events (myocardial infarction, stroke, or CV death);
all-cause death; and hospitalization for congestive heart failure.Results
Microalbuminuria was detected in 1140 (32.6%) of those with DM and 823
(14.8%) of those without DM at baseline. Microalbuminuria increased the adjusted
relative risk (RR) of major CV events (RR, 1.83; 95% confidence interval [CI],
1.64-2.05), all-cause death (RR, 2.09; 95% CI, 1.84-2.38), and hospitalization
for congestive heart failure (RR, 3.23; 95% CI, 2.54-4.10). Similar RRs were
seen for participants with or without DM, even after adjusting for other CV
risk factors (eg, the adjusted RR of the primary aggregate end point was 1.97
[95% CI, 1.68-2.31] in those with DM and 1.61 [95% CI, 1.36-1.90] in those
without DM).Compared with the lowest quartile of ACR (<0.22 mg/mmol), the
RRs of the primary aggregate end point in the second quartile (ie, ACR range,
0.22-0.57 mg/mmol) was 1.11 (95% CI, 0.95-1.30); third quartile, 1.38 (95%
CI, 1.19-1.60; ACR range, 0.58-1.62 mg/mmol); and fourth quartile, 1.97 (95%
CI, 1.73-2.25; ACR range, >1.62 mg/mmol) (P for trend
<.001, even after excluding those with microalbuminuria). For every 0.4-mg/mmol
increase in ACR level, the adjusted hazard of major CV events increased by
5.9% (95% CI, 4.9%-7.0%).Conclusions
Our results indicate that any degree of albuminuria is a risk factor
for CV events in individuals with or without DM; the risk increases with the
ACR, starting well below the microalbuminuria cutoff. Screening for albuminuria
identifies people at high risk for CV events.
Figures in this Article
Diabetes mellitus (DM) is a strong risk factor for cardiovascular (CV)
disease.1 Compared with those who do not have
DM, people with DM have a 2- to 4-fold increased risk of subsequent CV disease.2- 4 Risk factors that independently
increase CV risk in people with DM include smoking, hypertension, dyslipidemia,3 renal dysfunction,5
and hyperglycemia.6- 10
Recently, data from several studies have established microalbuminuria (MA),
or dipstick-negative albuminuria, as another CV risk factor. Microalbuminuria
is reported in approximately 30% of middle-aged patients with either type
1 or type 2 DM and in approximately 10% to 15% of middle-aged individuals
who do not have DM.11- 13
Although MA is associated with other risk factors in those with or without
DM,11,13- 14 it is
also an independent predictor of future strokes, death, and myocardial infarction
(MI).15- 19
Moreover, MA may also predict future congestive heart failure (CHF). However,
at present, there are few prospective data regarding this association.20- 23
Despite being increasingly recognized as a CV risk factor, the definition
of MA was based on its ability to predict diabetic nephropathy (ie, macroalbuminuria
or clinical proteinuria). Whether individuals with albumin excretion rates
below the MA threshold are also at risk for CV disease or whether there is
a progressive graded relationship between different degrees of albuminuria
and CV events is unclear.
Our study examines the relationship between baseline albuminuria levels
and future CV events using data collected from individuals with or without
DM enrolled in the Heart Outcomes Prevention Evaluation (HOPE) Study. Participants
were followed-up for a median of 4.5 years
To evaluate baseline risk factors for coronary artery disease in patients with type 2 diabetes mellitus.
A stepwise selection procedure, adjusting for age and sex, was used in 2693 subjects with complete data to determine which risk factors for coronary artery disease should be included in a Cox proportional hazards model.
3055 white patients (mean age 52) with recently diagnosed type 2 diabetes mellitus and without evidence of disease related to atheroma. Median duration of follow up was 7.9 years. 335 patients developed coronary artery disease within 10 years.
Angina with confirmatory abnormal electrocardiogram; non-fatal and fatal myocardial infarction.
Coronary artery disease was significantly associated with increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, and increased triglyceride concentration, haemoglobin A1c, systolic blood pressure, fasting plasma glucose concentration, and a history of smoking. The estimated hazard ratios for the upper third relative to the lower third were 2.26 (95% confidence interval 1.70 to 3.00) for low density lipoprotein cholesterol, 0.55 (0.41 to 0.73) for high density lipoprotein cholesterol, 1.52 (1.15 to 2.01) for haemoglobin A1c, and 1.82 (1.34 to 2.47) for systolic blood pressure. The estimated hazard ratio for smokers was 1.41 (1.06 to 1.88).
A quintet of potentially modifiable risk factors for coronary artery disease exists in patients with type 2 diabetes mellitus. These risk factors are increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, raised blood pressure, hyperglycaemia, and smoking.
Type 2 (non-insulin-dependent) diabetes is associated with a marked increase in the risk of coronary heart disease. It has been debated whether patients with diabetes who have not had myocardial infarctions should be treated as aggressively for cardiovascular risk factors as patients who have had myocardial infarctions.
To address this issue, we compared the seven-year incidence of myocardial infarction (fatal and nonfatal) among 1373 nondiabetic subjects with the incidence among 1059 diabetic subjects, all from a Finnish population-based study.
The seven-year incidence rates of myocardial infarction in nondiabetic subjects with and without prior myocardial infarction at base line were 18.8 percent and 3.5 percent, respectively (P<0.001). The seven-year incidence rates of myocardial infarction in diabetic subjects with and without prior myocardial infarction at base line were 45.0 percent and 20.2 percent, respectively (P<0.001). The hazard ratio for death from coronary heart disease for diabetic subjects without prior myocardial infarction as compared with nondiabetic subjects with prior myocardial infarction was not significantly different from 1.0 (hazard ratio, 1.4; 95 percent confidence interval, 0.7 to 2.6) after adjustment for age and sex, suggesting similar risks of infarction in the two groups. After further adjustment for total cholesterol, hypertension, and smoking, this hazard ratio remained close to 1.0 (hazard ratio, 1.2; 95 percent confidence interval, 0.6 to 2.4).
Our data suggest that diabetic patients without previous myocardial infarction have as high a risk of myocardial infarction as nondiabetic patients with previous myocardial infarction. These data provide a rationale for treating cardiovascular risk factors in diabetic patients as aggressively as in nondiabetic patients with prior myocardial infarction.
The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective randomized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications. The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy, retinopathy, and neuropathy.
The 470 hypertensive subjects, defined as having a baseline diastolic blood pressure of > or = 90 mmHg, were randomized to intensive blood pressure control (diastolic blood pressure goal of 75 mmHg) versus moderate blood pressure control (diastolic blood pressure goal of 80-89 mmHg).
The mean blood pressure achieved was 132/78 mmHg in the intensive group and 138/86 mmHg in the moderate control group. During the 5-year follow-up period, no difference was observed between intensive versus moderate blood pressure control and those randomized to nisoldipine versus enalapril with regard to the change in creatinine clearance. After the first year of antihypertensive treatment, creatinine clearance stabilized in both the intensive and moderate blood pressure control groups in those patients with baseline normo- or microalbuminuria. In contrast, patients starting with overt albuminuria demonstrated a steady decline in creatinine clearance of 5-6 ml.min-1.1.73 m-2 per year throughout the follow-up period whether they were on intensive or moderate therapy. There was also no difference between the interventions with regard to individuals progressing from normoalbuminuria to microalbuminuria (25% intensive therapy vs. 18% moderate therapy, P = 0.20) or microalbuminuria to overt albuminuria (16% intensive therapy vs. 23% moderate therapy, P = 0.28). Intensive therapy demonstrated a lower overall incidence of deaths, 5.5 vs. 10.7%, P = 0.037. Over a 5-year follow-up period, there was no difference between the intensive and moderate groups with regard to the progression of diabetic retinopathy and neuropathy. In addition, the use of nisoldipine versus enalapril had no differential effect on diabetic retinopathy and neuropathy.
Blood pressure control of 138/86 or 132/78 mmHg with either nisoldipine or enalapril as the initial antihypertensive medication appeared to stabilize renal function in hypertensive type 2 diabetic patients without overt albuminuria over a 5-year period. The more intensive blood pressure control decreased all-cause mortality.
To determine the relation between systolic blood pressure over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes.
Prospective observational study. Setting: 23 hospital based clinics in England, Scotland, and Northern Ireland.
4801 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk.
Primary predefined aggregate clinical outcomes: any complications or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, lower extremity amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photocoagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 10 mm Hg decrease in updated mean systolic blood pressure adjusted for specific confounders.
The incidence of clinical complications was significantly associated with systolic blood pressure, except for cataract extraction. Each 10 mm Hg decrease in updated mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes (95% confidence interval 10% to 14%, P<0.0001), 15% for deaths related to diabetes (12% to 18%, P<0.0001), 11% for myocardial infarction (7% to 14%, P<0.0001), and 13% for microvascular complications (10% to 16%, P<0.0001). No threshold of risk was observed for any end point.
In patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised blood pressure. Any reduction in blood pressure is likely to reduce the risk of complications, with the lowest risk being in those with systolic blood pressure less than 120 mm Hg.
To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes.
Prospective observational study. Setting: 23 hospital based clinics in England, Scotland, and Northern Ireland. Participants: 4585 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk.
Primary predefined aggregate clinical outcomes: any end point or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photo-coagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 1% reduction in updated mean HbA(1c) adjusted for possible confounders at diagnosis of diabetes.
The incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbA(1c) was associated with reductions in risk of 21% for any end point related to diabetes (95% confidence interval 17% to 24%, P<0.0001), 21% for deaths related to diabetes (15% to 27%, P<0.0001), 14% for myocardial infarction (8% to 21%, P<0.0001), and 37% for microvascular complications (33% to 41%, P<0.0001). No threshold of risk was observed for any end point.
In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA(1c) is likely to reduce the risk of complications, with the lowest risk being in those with HbA(1c) values in the normal range (<6.0%).
Microalbuminuria is a risk factor for cardiovascular (CV) events. The relationship between the degree of albuminuria and CV risk is unclear.
To estimate the risk of CV events in high-risk individuals with diabetes mellitus (DM) and without DM who have microalbuminuria and to determine whether levels of albuminuria below the microalbuminuria threshold increase CV risk.
The Heart Outcomes Prevention Evaluation study, a cohort study conducted between 1994 and 1999 with a median 4.5 years of follow-up.
Community and academic practices in North and South America and Europe.
Individuals aged 55 years or more with a history of CV disease (n = 5545) or DM and at least 1 CV risk factor (n = 3498) and a baseline urine albumin/creatinine ratio (ACR) measurement.
Cardiovascular events (myocardial infarction, stroke, or CV death); all-cause death; and hospitalization for congestive heart failure.
Microalbuminuria was detected in 1140 (32.6%) of those with DM and 823 (14.8%) of those without DM at baseline. Microalbuminuria increased the adjusted relative risk (RR) of major CV events (RR, 1.83; 95% confidence interval [CI], 1.64-2.05), all-cause death (RR, 2.09; 95% CI, 1.84-2.38), and hospitalization for congestive heart failure (RR, 3.23; 95% CI, 2.54-4.10). Similar RRs were seen for participants with or without DM, even after adjusting for other CV risk factors (eg, the adjusted RR of the primary aggregate end point was 1.97 [95% CI, 1.68-2.31] in those with DM and 1.61 [95% CI, 1.36-1.90] in those without DM). Compared with the lowest quartile of ACR (<0.22 mg/mmol), the RRs of the primary aggregate end point in the second quartile (ie, ACR range, 0.22-0.57 mg/mmol) was 1.11 (95% CI, 0.95-1.30); third quartile, 1.38 (95% CI, 1.19-1.60; ACR range, 0.58-1.62 mg/mmol); and fourth quartile, 1.97 (95% CI, 1.73-2.25; ACR range, >1.62 mg/mmol) (P for trend <.001, even after excluding those with microalbuminuria). For every 0.4-mg/mmol increase in ACR level, the adjusted hazard of major CV events increased by 5.9% (95% CI, 4.9%-7.0%).
Our results indicate that any degree of albuminuria is a risk factor for CV events in individuals with or without DM; the risk increases with the ACR, starting well below the microalbuminuria cutoff. Screening for albuminuria identifies people at high risk for CV events.
Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. The epidemic is chiefly of type 2 diabetes and also the associated conditions known as 'diabesity' and 'metabolic syndrome'. In conjunction with genetic susceptibility, particularly in certain ethnic groups, type 2 diabetes is brought on by environmental and behavioural factors such as a sedentary lifestyle, overly rich nutrition and obesity. The prevention of diabetes and control of its micro- and macrovascular complications will require an integrated, international approach if we are to see significant reduction in the huge premature morbidity and mortality it causes.
Complications of atherosclerosis cause most morbidity and mortality in patients with diabetes mellitus. Despite the frequency and severity of disease, proven medical therapy remains incompletely understood and underused.
To review the epidemiology, pathophysiology, and medical and invasive treatment of atherosclerosis in patients with diabetes mellitus.
Using the index terms diabetes mellitus, myocardial infarction, peripheral vascular diseases, cerebrovascular accident, endothelium, vascular smooth muscle, platelets, thrombosis, cholesterol, hypertension, hyperglycemia, insulin, angioplasty, and coronary artery bypass, we searched the MEDLINE and EMBASE databases from 1976 to 2001. Additional data sources included bibliographies of identified articles and preliminary data presented at recent cardiology conferences.
We selected original investigations and reviews of the epidemiology, pathophysiology, and therapy of atherosclerosis in diabetes. We selected randomized, double-blind, controlled studies, when available, to support therapeutic recommendations. Criteria for data inclusion (168 of 396) included publication in a peer-reviewed journal or presentation at a national cardiovascular society-sponsored meeting.
Data quality was determined by publication in peer-reviewed literature. Data extraction was performed by one of the authors.
Diabetes mellitus markedly increases the risk of myocardial infarction, stroke, amputation, and death. The metabolic abnormalities caused by diabetes induce vascular dysfunction that predisposes this patient population to atherosclerosis. Blood pressure control, lipid-lowering therapy, angiotensin-converting enzyme inhibition, and antiplatelet drugs significantly reduce the risk of cardiovascular events. Although diabetic patients undergo revascularization procedures because of acute coronary syndromes or critical limb ischemia, the outcomes are less favorable than in nondiabetic cohorts.
Since most patients with diabetes die from complications of atherosclerosis, they should receive intensive preventive interventions proven to reduce their cardiovascular risk.
'The Cost of Diabetes in Europe - Type II (CODE-2) study' provides the first coordinated attempt to assess the total costs of managing people with Type II (non-insulin-dependent) diabetes mellitus in Europe. Type II diabetes is associated with a number of serious long-term complications, which are a major cause of morbidity, hospitalisation and mortality in diabetic patients.
Patients were divided into four broad categories defining their complication status in terms of no complications, one or more microvascular complications, one or more macrovascular complications or one or more of each microvascular and macrovascular complication. The prevalence of complications and associated costs were assessed retrospectively for 6 months.
In total, 72% of patients in the CODE-2 study had at least one complication, with 19% having microvascular only, 10% having macrovascular only and 24% of the total having both microvascular and macrovascular complications. Of patients with microvascular complications, 28% had neuropathy, 20% renal damage, 20% retinopathy and 6.5% required treatment for eye complications. Among the patients with macrovascular complications, 18% had peripheral vascular disease, 17% angina, 12% heart failure and 9% had myocardial infarction. Percutaneous transluminal coronary angioplasty, coronary artery bypass graft or stroke occurred in 3%, 4% and 5% of the patients, respectively. In patients with both microvascular and macrovascular complications, the total cost of management was increased by up to 250% compared to those without complications.
Complications have a substantial impact on the costs of managing Type II diabetes. This study has confirmed that the prevention of diabetic complications will not only benefit patients, but potentially reduce overall healthcare expenditure.
To explore risk factors for all-cause mortality in patients with type 2 diabetes treated in primary care.
A prospective population-based study of 400 patients with type 2 diabetes who consecutively completed an annual checkup in primary care in Skara, Sweden, during 1992-1993. Vital status was ascertained to year 2000. Baseline characteristics as predictors for mortality were analyzed by Cox regression and expressed as relative risks (RRs), with 95% CIs.
During a mean follow-up time of 5.9 years, 131 patients died (56 deaths per 1,000 patients per year). In both sexes, all-cause mortality was predicted by HbA(1c) (by 1%; RR 1.14, 95% CI 1.01-1.27), and by LDL-to-HDL cholesterol ratios (1.15, 1.00-1.32). Increased mortality was also seen with prevalent hypertension (1.72, 1.21-2.44), microalbuminuria (1.87, 1.27-2.76), and previous cardiovascular disease (1.70, 1.15-2.50). Subanalyses revealed that increased mortality related to HbA(1c) was restricted to hypertensive patients with type 2 diabetes (1.23, 1.04-1.47). Serum triglycerides (by 1 mmol/l) predicted all-cause mortality in women (1.25, 1.06-1.47).
Poor glucose and lipid control and hypertension predicted all-cause mortality. Survival was also predicted by prevalent microalbuminuria and by previous cardiovascular disease. Confirming results from clinical trials, this population-based study has implications for primary and secondary prevention.
Background
Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension.
Methods
18 790 patients, from 26 countries, aged 50–80 years (mean 61·5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure ⩽90 mm Hg, 6264 to ⩽85 mm Hg, and 6262 to ⩽80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo.
Findings
Diastolic blood pressure was reduced by 20·3 mm Hg, 22·3 mm Hg, and 24·3 mm Hg, in the ⩽90 mm Hg, ⩽85 mm Hg, and ⩽80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82·6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86·5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group ⩽80 mm Hg compared with target group ⩽90 mm Hg (p for trend=0·005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0·03) and all myocardial infarction by 36% (p=0·002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0·001).
Interpretation
Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82·6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common.
Objective: To determine whether tight control of blood pressure with either a beta blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes. Design: Randomised controlled trial comparing an angiotensin converting enzyme inhibitor (captopril) with a beta blocker (atenolol) in patients with type 2 diabetes aiming at a blood pressure of < 150/ < 85 mm Hg. Setting 20 hospital based clinics in England, Scotland, and Northern Ireland. Subjects: 1148 hypertensive patients with type 2 diabetes(mean age 56 years, mean blood pressure 160/94 mm Hg). Of the 758 patients allocated to tight control of blood pressure, 400 were allocated to captopril and 358 to atenolol. 390 patients were allocated to less tight control of blood pressure. Main outcome measures: Predefined clinical end points, fatal and non-fatal, related to diabetes, death related to diabetes, and all cause mortality. Surrogate measures of microvascular and macrovascular disease included urinary albumin excretion and retinopathy assessed by retinal photography. Results: Captopril and atenolol were equally effective in reducing blood pressure to a mean of 144/83 mm Hg and 143/81 mm Hg respectively, with a similar proportion of patients (27% and 31%) requiring three or more antihypertensive treatments. More patients in the captopril group than the atenolol group took the allocated treatment: at their last clinic visit, 78% of those allocated captopril and 65% of those allocated atenolol were taking the drug (P < 0.0001). Captopril and atenolol were equally effective in reducing the risk of macrovascular end points. Similar proportions of patients in the true groups showed deterioration in retinopathy by two grades after nine years (31% in the captopril group and 37% in the atenolol group) and developed clinical grade albuminuria greater than or equal to 300 mg/l (5% and 9%). The proportion of patients with hypoglycaemic attacks was not different between groups, but mean weight gain in the atenolol group was greater (3.4 kg v 1.6 kg). Conclusion: Blood pressure lowering with captopril or atenolol was similarly effective in reducing the incidence of diabetic complications. This study provided no evidence that either drug has any specific beneficial or deleterious effect, suggesting that blood pressure reduction in itself may be more important than the treatment used.
The age-specific relevance of blood pressure to cause-specific mortality is best assessed by collaborative meta-analysis of individual participant data from the separate prospective studies. Methods Information was obtained on each of one million adults with no previous vascular disease recorded at baseline in 61 prospective observational studies of blood pressure and mortality. During 12.7 million person-years at risk, there were about 56 000 vascular deaths (12 000 stroke, 34000 ischaemic heart disease [IHD], 10000 other vascular) and 66 000 other deaths at ages 40-89 years. Meta-analyses, involving "time-dependent" correction for regression dilution, related mortality during each decade of age at death to the estimated usual blood pressure at the start of that decade. Findings Within each decade of age at death, the proportional difference in the risk of vascular death associated with a given absolute difference in usual blood pressure is about the same down to at least 115 mm Hg usual systolic blood pressure (SBP) and 75 mm Hg usual diastolic blood pressure (DBP), below which there is little evidence. At ages 40-69 years, each difference of 20 mm Hg usual SBP (or, approximately equivalently, 10 mm Hg usual DBP) is associated with more than a twofold difference in the stroke death rate, and with twofold differences in the death rates from IHD and from other vascular causes. All of these proportional differences in vascular mortality are about half as extreme at ages 80-89 years as at,ages 40-49 years, but the annual absolute differences in risk are greater in old age. The age-specific associations are similar for men and women, and for cerebral haemorrhage and cerebral ischaemia. For predicting vascular mortality from a single blood pressure measurement, the average of SBP and DBP is slightly more informative than either alone, and pulse pressure is much less informative. Interpretation Throughout middle and old age, usual blood pressure is strongly and directly related to vascular (and overall) mortality, without any evidence of a threshold down to at least 115/75 mm Hg.
This statement summarizes the recommendation of the third U.S. Preventive Services Task Force (USPSTF) for aspirin for the primary prevention of cardiovascular events, as well as the supporting scientific evidence. The complete information on which this statement is based, including evidence tables and references, can be found in a companion article in this issue. Copies of this document, the summary of the evidence, and the systematic evidence review can be obtained through the USPSTF Web site (http://www.ahrq.gov/clinic/uspstfix.htm) and in print through the Agency for Healthcare Research and Quality Publications Clearinghouse (800-358-9295).
Objective: To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes. Design: Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of < 150/85 mm Hg (with the use of an angiotensin converting enzyme inhibitor captopril or a β blocker atenolol as main treatment) with less tight control aiming at a blood pressure of < 180/105 mm Hg. Setting: 20 hospital based clinics in England, Scotland, and Northern Ireland. Subjects: 1148 hypertensive patients with type 2 diabetes (mean age 56, mean blood pressure at entry 160/94 mm Hg); 758 patients were allocated to tight control of blood pressure and 390 patients to less tight control with a medial follow up of 8.4 years. Main outcome measures: Predefined clinical end points, fatal and non-fatal, related to diabetes, deaths related to diabetes, and all cause mortality. Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography. Results: Mean blood pressure during follow up was significantly reduced in the group assigned tight blood pressure control (144/82 mm Hg) compared with the group assigned to less tight control (154/87 mm Hg) (P < 0.0001). Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24% in diabetes related end points (95% confidence interval 8% to 38%) (P = 0.0046), 32% in deaths related to diabetes (6% to 51%) (P = 0.019), 44% in strokes (11% to 65%) (P = 0.013), and 37% in microvascular end points (11% to 56%) (P = 0.0092), predominantly owing to a reduced risk of retinal photocoagulation. There was a non-significant reduction in all cause mortality. After nine years of follow up the group assigned to tight blood pressure control also had a 34% reduction in risk in the proportion of patients with deterioration of retinopathy by two steps (99% confidence interval 11% to 50%) (P = 0.0004) and a 47% reduced risk (7% to 70%) (P = 0.004) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study (ETDRS) chart. After nine years of follow up 29% of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures. Conclusion: Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinically important reduction in the risk of deaths related to diabetes, complications related to diabetes, progression of diabetic retinopathy, and deterioration in visual acuity.
Context Mortality from coronary heart disease has declined
substantially in the United States during the past 30 years. However,
it is unknown whether patients with diabetes have also experienced a
decline in heart disease mortality.
Objective To compare adults with diabetes with those without
diabetes for time trends in mortality from all causes, heart disease,
and ischemic heart disease.
Design, Setting, and Participants Representative cohorts of
subjects with and without diabetes were derived from the First National
Health and Nutrition Examination Survey (NHANES I) conducted between
1971 and 1975 (n=9639) and the NHANES I Epidemiologic
Follow-up Survey conducted between 1982 and 1984
(n=8463). The cohorts were followed up prospectively
for mortality for an average of 8 to 9 years.
Main Outcome Measure Changes in mortality rates per 1000
person-years for all causes, heart disease, and ischemic heart disease
for the 1982-1984 cohort compared with the 1971-1975 cohort.
Results For the 2 periods, nondiabetic men experienced a 36.4%
decline in age-adjusted heart disease mortality compared with a 13.1%
decline for diabetic men. Age-adjusted heart disease mortality declined
27% in nondiabetic women but increased 23% in diabetic women. These
patterns were also found for all-cause mortality and ischemic heart
disease mortality.
Conclusions The decline in heart disease mortality in the general
US population has been attributed to reduction in cardiovascular risk
factors and improvement in treatment of heart disease. The smaller
declines in mortality for diabetic subjects in the present study
indicate that these changes may have been less effective for people
with diabetes, particularly women.
Cardiovascular disease (CVD), particularly coronary heart disease (CHD), remains a major cause of mortality, morbidity, and disability in the US and other Westernized societies. As a result of therapeutic and preventive measures to control the CVD/CHD epidemic, mortality has declined steadily during the last several decades with a consequent gain in life expectancy, but the 1990s witnessed a slowing of this decline. In response to these trends, a range of therapeutic regimens were developed to address adverse CVD risk factor levels and their deleterious effects. The scientific evidence regarding the efficacy, cost effectiveness, strengths, and limitations of a range of pharmacologic and lifestyle approaches to CVD prevention — both primary and secondary — are reviewed in depth. Clinical trials aimed at primary and secondary prevention of CVD have documented the efficacy and cost effectiveness of various drugs in lowering individual risk factor levels and in reducing clinical CVD events. More recently, the idea of a ‘polypill’ containing low doses of multiple drugs has generated much interest, with proponents arguing that, given the high prevalence of CVD risk factors and the effectiveness of pharmacologic interventions, such a drug combination would reduce CHD mortality by 88% if taken by all individuals aged α55 years. However, current treatments to control high BP and serum cholesterol, while effective, do not typically reduce morbidity and mortality to levels observed in low-risk individuals, i.e. those with favorable levels of all readily measured major risk factors. Rather, primary prevention of all major risk factors starting early in life is critical. Prospective population-based research has delineated multiple long-term benefits associated with low-risk status in young adulthood and middle age, i.e. markedly lower age-specific CVD and total mortality rates, increased life expectancy, lower healthcare costs, lower medication use and prevalence of chronic diseases, and higher self-reported quality of life at older ages. Unfortunately, despite declines in the prevalence of most major CVD risk factors, low-risk status remains rare among US adults. Data have also demonstrated that adverse levels of one or more major risk factors precede clinical CHD in 90% or more of all cases, undermining the assertion that major CVD risk factors account for ‘no more than 50%’ of CHD cases. Hence, while numerous treatment options exist for secondary prevention of CVD, strategies that focus on progressively increasing the proportion of low-risk individuals could greatly reduce the need for secondary prevention in the first place. Public health policies must focus on prevention of all major risk factors simultaneously, using lifestyle approaches from early ages onwards to reduce population CVD risk to endemic levels, rather than current epidemic levels.
Data Synthesis: Meta-analysis was performed, and the quantitative results of the review were then used to model the consequences of treating patients with different levels of baseline risk for coronary heart disease. Five trials examined the effect of aspirin on cardiovascular events in patients with no previous cardiovascular disease. For patients similar to those enrolled in the trials, aspirin reduces the risk for the combined end point of nonfatal myocardial infarction and fatal coronary heart disease (summary odds ratio, 0.72 [95% CI, 0.60 to 0.87]). Aspirin increased the risk for hemorrhagic strokes (summary odds ratio, 1.4 [CI, 0.9 to 2.0]) and major gastrointestinal bleeding (summary odds ratio, 1.7 [CI, 1.4 to 2.1]). All-cause mortality (summary odds ratio, 0.93 [CI, 0.84 to 1.02]) was not significantly affected. For 1000 patients with a 5% risk for coronary heart disease events over 5 years, aspirin would prevent 6 to 20 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. For patients with a risk of 1% over 5 years, aspirin would prevent 1 to 4 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. Conclusions: The net benefit of aspirin increases with increasing cardiovascular risk. In the decision to use aspirin chemoprevention, the patient’s cardiovascular risk and relative utility for the different clinical outcomes prevented or caused by aspirin use must be considered.
The advanced lesions of atherosclerosis represent the culmination of a specialized form of chronic inflammation followed by a fibroproliferative process that takes place within the intima of the affected artery. Proliferation of smooth muscle cells and generation of connective tissue occur. Proliferation results from interactions between arterial smooth muscle, monocyte-derived macrophages, T lymphocytes, and endothelium. The initial lesion of atherosclerosis, the fatty streak, begins as an accumulation of monocytederived macrophages and T lymphocytes, which adhere and migrate into the intima of the affected artery. Smooth muscle cells, which are present in the intima or which migrate into the intima from the media, then replicate. Monocyte-derived macrophages and T cells also replicate during lesion formation and progression due to the production of cytokines and growth-regulatory molecules. These molecules determine whether there is proliferation and lesion progression or inhibition of proliferation and lesion regression. Several growthregulatory molecules may play critical roles in this process, including platelet-derived growth factor (PGDF), transforming growth factor beta, fibroblast growth factor, heparinbinding epidermal growth factor-like growth factor, and others. PDGF may be one of the principal components in this process because protein containing the PDGF B-chain has been demonstrated within activated lesion macrophages during every phase of atherogenesis. The presence of this growth factor and its receptors on lesion smooth muscle cells creates opportunities for smooth muscle chemotaxis and replication. Smooth muscle proliferation depends upon a series of complex signals based upon cellular interactions in the local microenvironment of the artery. The intracellular signalling pathways for mitogenesis versus chemotaxis are being investigated for smooth muscle. The roles of the cytokines and growth-regulatory peptides involved in these cellular interactions represent critical points of departure for intervention and the development of new diagnostic methods. In addition, magnetic resonance imaging has been developed to demonstrate the fine structure of lesions of atherosclerosis in peripheral arteries not subject to cardiac motion. This noninvasive methodology holds great promise for the future of these approaches.
Background and objective
Acetylsalicylic acid (ASA) has been recommended for primary (PP) and secondary prevention (SP) of cardiovascular disease (CVD) in diabetic patients. The consumption of ASA among Catalan diabetic people is described here.
Patients and method
We analyzed 1,718 questionnaires administered to members of the Catalonia’s Diabetic Association. ASA intake, history of CVD and medical advice about the use of ASA were evaluated.
Results
ASA was taken by 21% subjects (as PP in 14% and as SP in 53%). Medical advice had been received in 23% (15% as PP and 56% as SP).
Conclusions
ASA intake among diabetic patients is low in both PP and SP. Physicians should recommend its use to improve this situation.
Background and objective
A good metabolic control of patients with type 2 diabetes mellitus(DM2) will likely contribute to a decrease of their cardiovascular (CV) risk. Our aim was (1) toevaluate the degree of metabolic control with regard to glycemia, lipidemia and blood pressure(BP) and (2) to describe the prevalence of hypertension (HT) and hyperlipidemia in DM2 outpatients.
Patients and method
TranSTAR is an on-line, case-control, cross-sectional study, which wasperformed in outpatient from all around Spain. Data on basal glycemia (BG), glycosilated hemoglobin(A1C), lipid profile, BP and personal history of CV diseases were obtained. The postprandialglycemia (PPG) was measured in a capillary sample at 1-3 hours post-meal. Standardsof metabolic control of the Sociedad Española de Diabetes were applied to evaluate the degreeof glycemic, lipidemic and BP control.
Results
371 pairs of patients were studied. In DM2 patients, a bad control was observed in82.1% (CI 95%, 77.9–86.3) of them according to BG, in 88.4% (85.1–91.7) according to PPGand in 18.8% (14.3–23.3) according to A1C. An insufficient control in lipid profile was noticedin 63.3% (56.6–70.0) and in BP in 69.5% (64.2–74.8). 9.2% (0.9–17.5) and 20.5% (12.8–28.2) DM2 subjects had an unknown HT and hyperlipidemia, respectively.
Conclusion
The rate of DM2 outpatients with a bad metabolic control is very high. The availabilityof data from our own population should contribute to a better clinical management of thesepatients.
Background and objective
We aimed to assess the blood pressure (BP) control in patients withdiabetes mellitus (DM) treated in primary care (PC) and to establish the factors associated witha suboptimal control of BP.
Patients and method
This was a multicenter, transverse study. Ninety investigators included875 patients with DM (57.8% women), with a mean (SD) age of 64 (11.8) years. BP was measuredaccording to the Sixth Report of Joint National Committee (JNC-VI) and Word Health Organization/International Society Hypertension (WHO/ISH) recommendations, calculating thearithmetic mean of three consecutive measurements. Patients with a previous established diagnosiswere considered to be hypertensive, and an optimal control was considered when BP valueswere lower than 130/85 mmHg.
Results
66.7% (n = 583) patients with DM were previously diagnosed of hypertension (HT);86.3% (CI 95%: 83.0–89.1) of those with type 2 DM and 87.8% (CI95%: 70.9–96.0) of thosewith type 1 DM did not have an optimal control of BP at the visit (BP ≥ 130 and/or 85 mmHg).56.8% (CI 95%: 50.1–63.3) of those with type 2 DM and 23.8% (CI 95%: 12.6–39.8) of thosewith type 1 DM with unknown HT had a BP ≥ 130 and/or 85 mmHg at the visit. The medianof antihypertensive drugs used was 1 (1–2). In a multivariate analysis, age, higher body massindex (BMI), higher cholesterol levels and uric acid were associated with a worse BP control(p < 0.001).
Conclusions
In our study, 66.7% of patients with DM attended in PC had known HT and only 13.6% had an optimal BP control. Diabetic patients with HT were undertreated, with a medianof one antihypertensive drug.
Background
The term ‘metabolic syndrome’ refers to a clustering of specific cardiovascular disease (CVD) risk factors whose underlying pathophysiology is thought to be related to insulin resistance.
Methods
Since the term is widely used in research and clinical practice, we undertook an extensive review of the literature in relation to the syndrome’s definition, underlying pathogenesis, association with cardiovascular disease and to the goals and impact of treatment.
Discussion
While there is no question that certain CVD risk factors are prone to cluster, we found that the metabolic syndrome has been imprecisely defined, there is a lack of certainty regarding its pathogenesis, and there is considerable doubt regarding its value as a CVD risk marker. Our analysis indicates that too much critically important information is missing to warrant its designation as a ‘syndrome’.
Conclusion
Until much-needed research is completed, clinicians should evaluate and treat all CVD risk factors without regard to whether a patient meets the criteria for diagnosis of the ‘metabolic syndrome’.
Objective
To evaluate the effectiveness of the fixed dose of a lisinoprilhydrochlorothiazide combination treatment in the control of blood pressure, in poorly controlled high blood pressure people, treated with monotherapy.
Design
Prospective observational study.
Setting
Primary care frame.
Participants
931 patients (56.7% women) with an average age of 62.0±10.3 years, were included by 199 primary care physicians. 915 patients (98%) ended the study and finally they were included for the statistical analysis.
Main measurements
OMS/SIH recommendations on blood pressure measurement and diagnose of poor control were followed. Pulse pressure, body mass index and basic clinical analyses were assessed. Four continuation visits were made during six months.
Results
Lisinopril–hidrochlorothiazide (20/12.5 mg) reduced significantly SBP (24.6±3.5 mm Hg) and DBP (14,3±0.7 mm Hg) (P<.001). Blood pressure control was only influenced by age (OR, 0.81; 95% CI, 0.71-0.92; P=.001). Pulse pressure was reduced in 10.4±4.3 mm Hg (P<.001). After 24 weeks of treatment, glycemic and lipidic profiles showed an improvement, as well as HbA1c in diabetic people.
Conclusions
In Primary care, a 52.8% of poorly controlled with monotherapy high blood pressure people were controlled by a combination of lisinoprilhydrochlorothiazide (20/12.5 mg). In addition, pulse pressure was decreased and both lipid and glucose blood profiles improved.
To estimate the prevalence of and the cardiovascular risk associated with the metabolic syndrome using the new definition proposed by the World Health Organization
A total of 4,483 subjects aged 35-70 years participating in a large family study of type 2 diabetes in Finland and Sweden (the Botnia study) were included in the analysis of cardiovascular risk associated with the metabolic syndrome. In subjects who had type 2 diabetes (n = 1,697), impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) (n = 798) or insulin-resistance with normal glucose tolerance (NGT) (n = 1,988), the metabolic syndrome was defined as presence of at least two of the following risk factors: obesity, hypertension, dyslipidemia, or microalbuminuria. Cardiovascular mortality was assessed in 3,606 subjects with a median follow-up of 6.9 years.
In women and men, respectively, the metabolic syndrome was seen in 10 and 15% of subjects with NGT, 42 and 64% of those with IFG/IGT, and 78 and 84% of those with type 2 diabetes. The risk for coronary heart disease and stroke was increased threefold in subjects with the syndrome (P < 0.001). Cardiovascular mortality was markedly increased in subjects with the metabolic syndrome (12.0 vs. 2.2%, P < 0.001). Of the individual components of the metabolic syndrome, microalbuminuria conferred the strongest risk of cardiovascular death (RR 2.80; P = 0.002).
The WHO definition of the metabolic syndrome identifies subjects with increased cardiovascular morbidity and mortality and offers a tool for comparison of results from diferent studies.
LR: 20061115; JID: 7501160; 0 (Antilipemic Agents); 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 57-88-5 (Cholesterol); CIN: JAMA. 2001 Nov 21;286(19):2401; author reply 2401-2. PMID: 11712930; CIN: JAMA. 2001 Nov 21;286(19):2400-1; author reply 2401-2. PMID: 11712929; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712928; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712927; CIN: JAMA. 2001 May 16;285(19):2508-9. PMID: 11368705; CIN: JAMA. 2003 Apr 16;289(15):1928; author reply 1929. PMID: 12697793; CIN: JAMA. 2001 Aug 1;286(5):533-5. PMID: 11476650; CIN: JAMA. 2001 Nov 21;286(19):2401-2. PMID: 11712931; ppublish
Subjects with diabetes have a greatly increased risk of CHD, which is only partially related to their elevated glucose. Other factors such as insulin resistance and dyslipidemia are likely to be important. The type of dyslipidemia that is most characteristic of type 2 diabetic subjects is elevated triglycerides and decreased HDL cholesterol levels, although all lipoproteins have compositional abnormalities. Surprisingly few good prospective studies of lipoprotein levels in relation to CHD have been done in diabetic subjects. Available studies suggest that low HDL cholesterol may be the most important risk factor for CHD in observational studies. In studies in which total cholesterol and triglyceride were done, cholesterol and triglycerides were risk factors for CHD, although triglycerides were often a stronger predictor. However, the strength of triglyceride as a risk factor for CHD may depend partially on its association with other variables (e.g., hypertension, plasminogen activator inhibitor 1 [PAI-1], etc.). In clinical trials in diabetic subjects, LDL reduction with statins has led to significant reductions in CHD incidence. In addition, overall mortality was reduced with statin therapy, although the results were not statistically significant. Gemfibrozil has led to reductions in CHD incidence in diabetic subjects, although the results were not statistically significant perhaps because of low sample size. Regarding lipoproteins and CHD risk in diabetic patients, the very positive results of statin trials point to LDL cholesterol being more important than previous realized. Apparently, having a borderline high LDL cholesterol (between 130 and 160 mg/dl) in a diabetic patient is equivalent to a much higher LDL cholesterol in terms of CHD risk for a nondiabetic subject. Therefore, the primary target of therapy in diabetic patients is lowering LDL cholesterol (or possibly, non-HDL cholesterol). Statins are the preferred pharmacological agent in this situation. Once LDL cholesterol levels have been lowered, attention can be given to treatment of residual hypertriglyceridemia and low HDL. The goal here is weight reduction and increased exercise. However, for selected patients, combining a fibric acid (or low-dose nicotinic acid) with a statin also can be considered. Reduction of LDL levels should take priority over reduction of triglycerides in combined hyperlipidemia because of the proven safety of the statin class of drugs as well as greater reduction in CHD incidence.
Mortality from coronary heart disease has declined substantially in the United States during the past 30 years. However, it is unknown whether patients with diabetes have also experienced a decline in heart disease mortality.
To compare adults with diabetes with those without diabetes for time trends in mortality from all causes, heart disease, and ischemic heart disease.
Representative cohorts of subjects with and without diabetes were derived from the First National Health and Nutrition Examination Survey (NHANES I) conducted between 1971 and 1975 (n = 9639) and the NHANES I Epidemiologic Follow-up Survey conducted between 1982 and 1984 (n = 8463). The cohorts were followed up prospectively for mortality for an average of 8 to 9 years.
Changes in mortality rates per 1000 person-years for all causes, heart disease, and ischemic heart disease for the 1982-1984 cohort compared with the 1971-1975 cohort.
For the 2 periods, nondiabetic men experienced a 36.4% decline in age-adjusted heart disease mortality compared with a 13.1% decline for diabetic men. Age-adjusted heart disease mortality declined 27% in nondiabetic women but increased 23% in diabetic women. These patterns were also found for all-cause mortality and ischemic heart disease mortality.
The decline in heart disease mortality in the general US population has been attributed to reduction in cardiovascular risk factors and improvement in treatment of heart disease. The smaller declines in mortality for diabetic subjects in the present study indicate that these changes may have been less effective for people with diabetes, particularly women.
This statement examines the cardiovascular complications of diabetes mellitus and considers opportunities for their prevention. These complications include coronary heart disease (CHD), stroke, peripheral arterial disease, nephropathy, retinopathy, and possibly neuropathy and cardiomyopathy. Because of the aging of the population and an increasing prevalence of obesity and sedentary life habits in the United States, the prevalence of diabetes is increasing. Thus, diabetes must take its place alongside the other major risk factors as important causes of cardiovascular disease (CVD). In fact, from the point of view of cardiovascular medicine, it may be appropriate to say, “diabetes is a cardiovascular disease.”
The most prevalent form of diabetes mellitus is type 2 diabetes. This disorder typically makes its appearance later in life. The underlying metabolic causes of type 2 diabetes are the combination of impairment in insulin-mediated glucose disposal (insulin resistance) and defective secretion of insulin by pancreatic β-cells. Insulin resistance develops from obesity and physical inactivity, acting on a substrate of genetic susceptibility.1 2 Insulin secretion declines with advancing age,3 4 and this decline may be accelerated by genetic factors.5 6 Insulin resistance typically precedes the onset of type 2 diabetes and is commonly accompanied by other cardiovascular risk factors: dyslipidemia, hypertension, and prothrombotic factors.7 8 The common clustering of these risk factors in a single individual has been called the metabolic syndrome. Many patients with the metabolic syndrome manifest impaired fasting glucose (IFG)9 even when they do not have overt diabetes mellitus.10 The metabolic syndrome commonly precedes the development of type 2 diabetes by many years11 ; of great importance, the risk factors that constitute this syndrome contribute independently to CVD risk.
Recently, new criteria have been accepted for the diagnosis of diabetes.9 The upper threshold of fasting plasma glucose for the …
Despite the numerous studies on the relation of albuminuria with increased risk of all-cause mortality in type 2 diabetes mellitus, it remains uncertain whether microalbuminuria and/or gross proteinuria are independent risk factors for cardiovascular mortality. Moreover, the association of albuminuria with cardiovascular mortality in people with type 2 diabetes mellitus has not been well described in US populations.
To estimate the relative risks (RRs) for the associations of microalbuminuria and gross proteinuria with cardiovascular disease mortality among persons with older-onset diabetes mellitus.
We conducted a prospective cohort study of 840 people with older-onset diabetes mellitus who provided urine samples in the 1984-1986 examination of a population-based study of diabetic persons. The presence of microalbuminuria was determined by an agglutination inhibition assay and gross proteinuria by a reagent strip. The main outcome was time to mortality from cardiovascular disease, as determined from death certificates.
Of the 840 older-onset diabetic persons, 54.8% had normoalbuminuria, while 24.8% had microalbuminuria and 20.5% had gross proteinuria. During the 12-year follow-up (6127 person-years), we identified 364 deaths from cardiovascular disease. Compared with persons with normoalbuminuria, those with microalbuminuria and gross proteinuria had significantly higher risks of cardiovascular mortality. The RR as controlled for age, sex, glycemic control, insulin use, alcohol intake, physical activity, cardiovascular disease history, antihypertensive use, and retinopathy severity, was 1.84 (95% confidence interval [CI], 1.42-2.40) for those with microalbuminuria and 2.61 (95% CI, 1.99-3.43) for those with gross proteinuria. Further adjustment for other factors did not change the relations we found. When the end point used was mortality from coronary heart disease, stroke, or all causes, the increased risks were significant for both microalbuminuria (adjusted RRs [95% CIs], 1.96 [1.42-2.72], 2.20 [1.29-3.75], and 1.68 [1.35-2.09], respectively) and gross proteinuria (adjusted RRs [95% CIs], 2.73 [1.95-3.81], 2.33 [1.28-4.24], and 2.47 [1.97-3.10], respectively).
Results from our population-based study strongly suggest that both microalbuminuria and gross proteinuria were significantly associated with subsequent mortality from all causes and from cardiovascular, cerebrovascular, and coronary heart diseases. These associations were independent of known cardiovascular risk factors and diabetes-related variables.
The use of aspirin to prevent cardiovascular disease events in patients without a history of cardiovascular disease is controversial.
To examine the benefits and harms of aspirin chemoprevention.
MEDLINE (1966 to May 2001).
1) Randomized trials at least 1 year in duration that examined aspirin chemoprevention in patients without previously known cardiovascular disease and 2) systematic reviews, recent trials, and observational studies that examined rates of hemorrhagic strokes and gastrointestinal bleeding secondary to aspirin use.
One reviewer read and extracted data from each included article and constructed evidence tables. A second reviewer checked the accuracy of the data extraction. Discrepancies were resolved by consensus.
Meta-analysis was performed, and the quantitative results of the review were then used to model the consequences of treating patients with different levels of baseline risk for coronary heart disease. Five trials examined the effect of aspirin on cardiovascular events in patients with no previous cardiovascular disease. For patients similar to those enrolled in the trials, aspirin reduces the risk for the combined end point of nonfatal myocardial infarction and fatal coronary heart disease (summary odds ratio, 0.72 [95% CI, 0.60 to 0.87]). Aspirin increased the risk for hemorrhagic strokes (summary odds ratio, 1.4 [CI, 0.9 to 2.0]) and major gastrointestinal bleeding (summary odds ratio, 1.7 [CI, 1.4 to 2.1]). All-cause mortality (summary odds ratio, 0.93 [CI, 0.84 to 1.02]) was not significantly affected. For 1000 patients with a 5% risk for coronary heart disease events over 5 years, aspirin would prevent 6 to 20 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events. For patients with a risk of 1% over 5 years, aspirin would prevent 1 to 4 myocardial infarctions but would cause 0 to 2 hemorrhagic strokes and 2 to 4 major gastrointestinal bleeding events.
The net benefit of aspirin increases with increasing cardiovascular risk. In the decision to use aspirin chemoprevention, the patient's cardiovascular risk and relative utility for the different clinical outcomes prevented or caused by aspirin use must be considered.
First-degree relatives of patients with Type I (insulin-dependent) diabetes mellitus diagnosed at 20 years of age or under were screened for islet cell antibodies (ICA) in the course of recruitment to an international diabetes prevention trial. Our aim was to evaluate the influence of age, gender, proband characteristics and nationality on the prevalence of ICA and co-existence of autoantibodies to GAD, IA-2 and insulin.
A central laboratory screened samples from 10 326 non-diabetic relatives who were aged less than 40 years, from eight European countries for ICA. Antibodies to GAD and IA-2 were measured in all samples with ICA of 10 JDF units or more.
Overall, 8.9 % of relatives had ICA of 10 JDF units or more, 3.8 % with ICA of 20 JDF units or more. Of 921 relatives with ICA of 10 JDF units or more, 29 % had co-existing antibodies to GAD or IA-2 or both. ICA of 10 JDF units or more were more prevalent in males (10.8 %) than females (7.3 %). ICA with GAD or IA-2 antibodies or both were also more common in males (3.4 %) than females (1.9 %) and in relatives under 20 years of age (3.5 % vs 1.5 %). Multiple regression analysis showed nationality to be a determinant of ICA of 10 JDF units or more but not of ICA of 20 JDF units or more or of ICA with co-existing islet antibodies, and confirmed the importance of age and gender as determinants of islet autoimmunity.
Relatives from different European countries have similar rates of islet autoimmunity despite wide variation in the background incidence of childhood diabetes, and male excess is equally evident in all populations. The male excess of ICA and islet autoimmunity over 10 years of age reflects the higher male incidence of Type I diabetes in this age group, and suggests that boys may be more likely than girls to develop islet autoimmunity during adolescence.
Using epidemiological and clinical trial evidence, the sixth report of the Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure (JNC-VI) updated previous guidelines to suggest that in addition to blood pressure, decisions on initial treatment should emphasize absolute cardiovascular disease risk. We estimated the impact of using cardiovascular disease risk on treatment recommendations for the US population using data from 16 527 participants in the Third National Health and Nutrition Examination Survey. In the US population > or =20 years of age, 36% (62 million) had high-normal blood pressure or greater (systolic/diastolic blood pressure > or =130 mm Hg/> or =85 mm Hg) or were taking antihypertensive medication. Of this population, 5.1% (3.2 million) were stratified into risk group A (no cardiovascular disease risk factors or prevalent cardiovascular disease), 66.3% (41.4 million) into risk group B (> or =1 major risk factor), and 28.6% (17.9 million) into risk group C (diabetes mellitus, clinical cardiovascular disease, target organ damage). Also, 26% of this group (16.2 million) had high-normal blood pressure and were in risk groups A or B, a context in which vigorous lifestyle modification is recommended in the JNC-VI guidelines. Additionally, 11% (7.0 million) had high-normal blood pressure (systolic/diastolic, 130 to 139 mm Hg/85 to 89 mm Hg, respectively) or stage-1 hypertension (140 to 159 mm Hg/90 to 99 mm Hg), and at least 1 factor, placing them in risk group C, but they were not currently on antihypertensive medication. JNC-VI, but not previous JNC guidelines, specifically recommends drug therapy as initial treatment for these patients. We conclude that JNC-VI refines cardiovascular risk and enfranchises more Americans to undertake more aggressive risk reduction maneuvers.
'The Cost of Diabetes in Europe - Type II study' is the first coordinated attempt to measure total healthcare costs of Type II (non-insulin-dependent) diabetes mellitus in Europe. The study evaluated more than 7000 patients with Type II diabetes in eight countries -- Belgium, France, Germany, Italy, the Netherlands, Spain, Sweden and the United Kingdom.
A bottom-up, prevalence-based design was used, which optimised the collection of data at the national level while maintaining maximum international comparability. Effort was made to ensure consistency in terms of data specification, data collection tools and methods, sampling design, and the analysis and reporting of results. Results are reported for individual countries and in aggregate for the total study population.
The total direct medical costs of Type II diabetes in the eight European countries was estimated at EUR 29 billion a year (1999 values). The estimated average yearly cost per patient was EUR 2834 a year. Of these costs, hospitalisations accounted for the greatest proportion (55%, range 30-65%) totalling EUR 15.9 billion for the eight countries. During the 6-month evaluation period, 13% of the Type II diabetic patients were hospitalised, with an average of 23 days in hospital projected annually. In contrast, drug costs for managing Type II diabetes were relatively low, with antidiabetic drugs and insulin accounting for only 7% of the total healthcare costs for Type II diabetes.
Type II diabetes mellitus is a common disease and the prevalence is expected to increase considerably in the future, especially in developing countries. Current comprehensive economic data on the costs of diabetes are required for policy decisions to optimise resource allocation and to evaluate different approaches for disease management.
An analysis of the 3,866 diabetic patients from the CAPRIE study revealed that they had a much higher rate of recurrent ischemic events than nondiabetic patients and that the benefit of clopidogrel over aspirin was amplified in the diabetic cohort. The level of risk and degree of benefit were highest in those diabetic patients who received insulin therapy.