Impaired fibrinolysis and risk for cardiovascular disease in the metabolic syndrome and type 2 diabetes

Patients with the metabolic syndrome are insulin resistant and manifest a cluster of risk factors for cardiovascular disease. Impaired fibrinolysis and increased concentrations in blood of plasminogen activator inhibitor-1 (PAI-1) are related to insulin resistance and abdominal obesity and may contribute to the increased risk for cardiovascular disease in this group. Weight loss, metformin, and thiazolidinediones ameliorate insulin resistance and decrease concentrations of PAI-1. Thus, they may lower risk in patients with the metabolic syndrome.     

Oxidative stress biomarkers in type 2 diabetes mellitus for assessment of cardiovascular disease risk

Aims

Type-2 Diabetes Mellitus (T2DM) is one of the most prevalent and progressive metabolic conditions affecting approximately 8.5% of the global population. Individuals with T2DM have a significantly increased risk of developing chronic conditions such as cardiovascular disease (CVD) and its associated complications, therefore, it is of great importance to establish strategies for combatting T2DM and its associated chronic conditions. Current literature has identified several biomarkers that are known to play a key role in the pathogenesis of CVD. Many of these biomarkers affecting CVD are influenced by an increase in oxidative stress as seen in T2DM. The purpose of this review is to analyse and correlate the oxidative stress-related biomarkers that have been identified in the literature to provide an updated summary of their significance in CVD risk factors.

Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents

Overweight/obesity continues to increase in children and adolescents, and annual obesity-related hospital costs in 6-17 yr olds have reached 127 million dollars per year. Overweight children and adolescents are now being diagnosed with impaired glucose tolerance and type 2 diabetes, and they show early signs of the insulin resistance syndrome and cardiovascular risk. Several risk factors have been identified as contributors to the development of type 2 diabetes and cardiovascular risk in youth. These factors include increased body fat and abdominal fat, insulin resistance, ethnicity (with greater risk in African-American, Hispanic, and Native American children), and onset of puberty. There is no clear explanation of how these factors increase risk, but they appear to act in an additive fashion. We hypothesize that the constellation of these risk factors may be especially problematic during the critical period of adolescent development, especially in individuals who may have compromised beta-cell function and an inability to compensate for severe insulin resistance. Therefore, the purpose of this paper is to review the pathophysiology of type 2 diabetes and cardiovascular risk in obese children and adolescents.     

Meta-analysis of type 1 diabetes mellitus and risk of cardiovascular disease

BackgroundIndividuals with diabetes have a high risk of cardiovascular disease (CVD). However, the association between type 1 diabetes mellitus (T1DM) and the risk of CVD has not been well addressed. This meta-analysis aimed to investigate the association between T1DM and CVD.MethodsWe searched the PubMed and EMBASE for studies that examined the association between T1DM and CVD until October 2020. We calculated the pooled risk ratios (RRs) with confidence intervals (CIs) from individual studies based on a random-effects model.ResultsWe included 10 observational studies involving 166,027 patients with T1DM, and individuals were matched controls from the general population. Among T1DM patients, the RR of CVD was 5.09 (95% CI, 3.72–6.96), of coronary heart disease (CHD) was 9.38 (95% CI, 5.56–15.82), and of myocardial infarction was 6.37 (95% CI, 3.81–10.66). The RR of heart failure was 4.29 (95% CI, 3.54–5.19), of atrial fibrillation was 1.36 (95% CI, 1.17–1.59), and of stroke was 4.08 (95% CI, 3.42–4.86). Moreover, there was an increased RR among females for CHD, CVD, myocardial infarction, and stroke associated with T1DM.ConclusionsThis study suggests that T1DM is associated with an increased risk of several types of CVD. However, the possible mechanisms for the increased risk of CVD remain unclear.     

Microalbuminuria and cardiovascular risk factors in type 2 diabetes mellitus

Prospective studies have shown that increased urinary albumin excretion is a risk factor for cardiovascular morbidity and mortality in patients with Type 2 diabetes mellitus, but the nature of the association remains unknown. Eighty-five patients aged less than 65 years and not treated with insulin were studied. The overnight albumin excretion rate (AER) was measured in each patient and analysed in relation to several putative risk factors for cardiovascular disease. AER was used both as a continuous variable and after dividing patients into high-risk (AER greater than or equal to 10 micrograms min-1) and low-risk (AER less than 10 micrograms min-1) groups. By both methods of analysis AER was significantly correlated with both seated and supine diastolic blood pressure levels and with resting heart rate. Body mass index and waist-hip ratio appeared higher and HDL-cholesterol lower in the at-risk group, but differences were not statistically significant. The level of Factor VII was not significantly lower in the at-risk group. Little of the cardiovascular risk associated with raised AER can be attributed to associations with conventional risk factors.     

2型糖尿病合并冠心病患者心血管危险因素控制现状的调查

目的:根据指南要求,调查2型糖尿病合并冠心病患者主要心血管危险因素的控制情况,分析影响血糖的相关因素。方法:采用横断面调查方法,对收集的2型糖尿病合并冠心病者421例进行问卷调查、体格检查及血液检查,以获取一般资料、血糖、血压、血脂及体质量等。按指南标准计算各指标达标率。结果:HbA1c、收缩压、舒张压、HDL-C、TG、LDL-C和BMI的达标率,分别是61.9%、43.2%、69.3%、62.4%(男性)/50.1%(女性)、43.3%、63.1%和29.1%(男性)/32.9%(女性)。影响血糖的因素有饮食运动控制、规律用药和知晓血糖控制目标。结论:2型糖尿病合并冠心病患者控制现状与指南要求仍有差距,可通过加强患者的自我管理和糖尿病知识的认知,提高治疗质量。     

Exercise, fitness, and cardiovascular disease risk in type 2 diabetes and the metabolic syndrome

This article highlights research supporting the concept that increased physical activity and cardiorespiratory fitness attenuate risk of cardiovascular disease, type 2 diabetes, and the metabolic syndrome. Increased activity and fitness also attenuate risk of developing cardiovascular disease in persons who have type 2 diabetes or the metabolic syndrome. Although controversial, relationships between physical activity/physical fitness and type 2 diabetes/metabolic syndrome are largely independent of body weight. Thus, physical inactivity and poor cardiorespiratory fitness are not only important determinants of cardiovascular and metabolic diseases, but they can also be considered common features of these conditions, much like traditional risk factors such as obesity and insulin resistance.     

Do primary health care nurses address cardiovascular risk in diabetes patients?

AimsTo identify factors associated with assessment and nursing management of blood pressure, smoking and other major cardiovascular risk factors by primary health care nurses in Auckland, New Zealand.MethodsPrimary health care nurses (n = 287) were randomly sampled from the total (n = 1091) identified throughout the Auckland region and completed a self-administered questionnaire (n = 284) and telephone interview. Nurses provided details for 86% (n = 265) of all diabetes patients they consulted on a randomly selected day.ResultsThe response rate for nurses was 86%. Of the patients sampled, 183 (69%) patients had their blood pressure measured, particularly if consulted by specialist (83%) and practice (77%) nurses compared with district (23%, p = 0.0003). After controlling for demographic variables, multivariate analyses showed patients consulted by nurses who had identified stroke as a major diabetes-related complication were more likely to have their blood pressure measured, and those consulted by district nurses less likely. Sixteen percent of patients were current smokers. Patients consulted by district nurses were more likely to smoke while, those >66 years less likely. Of those who wished to stop, only 50% were offered nicotine replacement therapy. Patients were significantly more likely to be advised on diet and physical activity if they had their blood pressure measured (p < 0.0001).ConclusionsMeasurement of blood pressure and advice on diet or physical activity were not related to patient's cardiovascular risk profile and management of smoking cessation was far from ideal. Education of the community-based nursing workforce is essential to ensure cardiovascular risk management becomes integrated into diabetes management.     

Chronic kidney disease in type 2 diabetes: Implications for managing glycaemic control,cardiovascular and renal risk

This review examines the current literature relating to diabetes related kidney disease (DKD) and the optimal management of cardio-renal risk. DKD develops in approximately 40% of patients with type 2 diabetes mellitus. The mainstay of therapy is to reduce the progression of DKD by optimising hyperglycaemia, blood pressure, lipids and lifestyle. Evidence supports the role for renin-angiotensin system blockade in limiting the progression of DKD. Recent data from diabetes related cardiovascular outcome trials and renal specific trials have provided a novel insight on the additional benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in reducing the progression of DKD as well as cardiovascular risk. Lessons have been learnt from CREDENCE and there are expectations that DAPA-CKD and EMPA-KIDNEY will further support the benefits of SGLT2 inhibition in relation to DKD. As a consequence, international guidelines have been updated to reflect the positive benefits. In addition, novel steroidal mineralocorticoid receptor antagonists offer a potential role in future years. The review examines the current evidence and future approach to optimising outcomes for renal protection in patients with diabetes.     

Asymmetric dimethylarginine as a risk factor for cardiovascular disease in Japanese patients with type 2 diabetes mellitus

Aims Although asymmetric dimethylarginine (ADMA) is known to be involved in the developing process of cardiovascular diseases (CVD), little is known about the effects of ADMA on atherosclerosis in Asian patients with diabetes , who have the racial feature of lower body mass index (BMI) and decreased capacity of insulin secretion and sensitivity. Methods We employed 55 Japanese patients with type 2 diabetes mellitus (mean age, 64·2 years; 56% men) in a 6‐month‐longitudinal study and 450 patients (mean age, 62·7 years; 56% men) in a cross‐sectional study and examined the association of serum ADMA with atherosclerosis parameters [intima‐media thickness (IMT) and brachial‐ankle pulse wave velocity (baPWV)] as well as with the presence of CVD. Results In the longitudinal study, multiple regression analysis showed that basal serum ADMA level had a significantly positive association with changes in IMT (β = 0·35, P = 0·03) independently of age, duration of diabetes, BMI, blood pressure, low‐density lipoprotein and high‐density lipoprotein (LDL and HDL) cholesterol, HbA_1c, and renal function. In the cross‐sectional study, the serum ADMA level was significantly and positively associated with the presence of CVD (odds ratio = 7·22, 95% confidence interval 1·29–40·40, P = 0·02, by logistic analysis) and with baPWV (β = 0·14, P < 0·01, by multiple regression analysis). In contrast, serum symmetric dimethylarginine level, a structural isomer of ADMA, was associated neither with parameters for atherosclerosis nor with the presence of CVD in both studies. Conclusions Serum ADMA is a predictor of atherosclerosis and associated with the presence of CVD in Japanese patients with type 2 diabetes mellitus.     

Limited benefit of haemoglobin glycation index as risk factor for cardiovascular disease in type 2 diabetes patients

BackgroundThe haemoglobin glycation index (HGI) has been proposed as a marker of interindividual differences in haemoglobin glycosylation. Previous studies have shown a relationship between high HGI and risk of cardiovascular disease (CVD) in patients with diabetes. However, no studies have investigated the role of previous CVD in this association.MethodsThe study cohort comprised patients with type 2 diabetes mellitus (T2DM; n = 1910) included in the Second Manifestations of Arterial Disease (SMART) study. The relationship between either HGI or HbA_1c and a composite of cardiovascular events as the primary outcome, and mortality, cardiovascular mortality, myocardial infarction and stroke as secondary outcomes, was investigated using Cox proportional-hazards models. Similar analyses were performed after stratification according to previous CVD.ResultsA 1-unit higher HGI was associated with a 29% greater risk of a composite of cardiovascular events (HR: 1.29, 95% CI: 1.06–1.57) in patients without previous CVD, whereas no such relationship was seen in patients with previous CVD (HR: 0.96, 95% CI: 0.86–1.08). The direction and magnitude of the hazard ratios (HRs) of HGI and HbA_1c in relation to outcomes were similar. Additional adjustment for HbA_1c in the association between HGI and outcomes lowered the HRs.ConclusionSimilar to HbA_1c, higher HGI is related to higher risk of cardiovascular events in patients with T2DM without CVD. As HbA_1c has proved to be a comparable risk factor, and obtaining and interpreting the HGI is complicated, any additional benefit of applying the HGI in clinical settings is likely to be limited.     

2型糖尿病家系青少年一级亲属心血管危险因素研究

目的探讨2型糖尿病（T2DM）家族史对青少年心血管危险因素的影响。方法秦皇岛地区12～18岁青少年4023人横断面调查。根据父母有无糖尿病分为糖尿病家族史阳性组（FH＋）和阴性组（FH-）。测量腰围（WC）、血压、FPG、血脂,计算BMI。结果（1）FH＋组腰围、FPG、TC和LDL-C均高于FH-组（P〈0.05）,超重/肥胖、高SBP、高FPG检出率高于FH-组（P〈0.05）。（2）校正年龄、性别后FH＋组SBP、FPG升高、超重/肥胖的危险性分别是FH-组的1.54、2.06、1.33倍,95%CI分别是（1.10～2.16）、（1.46～2.89）、（1.12～1.59）,具有2项以上心血管危险因素的危险性是FH-组的1.72倍。结论T2DM患者的青少年一级亲属已存在心血管危险因素增加和聚集。应重视对这一人群进行早期筛查和干预,以减少心血管病的发生。     

Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease

CONTEXT: Metabolic risk conferred by adiposity may be due to associated risk factor clustering. OBJECTIVE: The objective of this study was to assess risk for diabetes or cardiovascular disease (CVD) stratified by body mass index (BMI) and the presence or absence of metabolic syndrome (MetS) or insulin resistance (IR). DESIGN, SETTING, AND PARTICIPANTS: This was a community-based, longitudinal study of 2902 people (55% women, mean age 53 yr) without diabetes or CVD in 1989-1992 followed for up to 11 yr. We categorized subjects by normal weight (BMI < 25 kg/m(2)), overweight (25-29.9 kg/m(2)), or obese (>30 kg/m(2)) and by the National Cholesterol Education Program's Adult Treatment Panel MetS or the top quartile of homeostasis model IR. We used proportional hazard models to estimate risk relative to normal weight and no MetS or IR. MAIN OUTCOME MEASURE: Incident type 2 diabetes (treatment or fasting glucose > or = 7 mmol/liter, 141 events) or CVD (myocardial infarction, stroke, or claudication, 252 events) were measured. RESULTS: Among 1056 normal-weight subjects, 7% had MetS and a risk factor-adjusted relative risk for diabetes of 3.97 (95% confidence interval, 1.35-11.6) and for CVD of 3.01 (1.68-5.41). Among 638 obese subjects, 37% did not have MetS or significantly increased risk. Obese subjects with MetS had an adjusted relative risk for diabetes of 10.3 (5.44-19.5) and for CVD of 2.13 (1.43-3.18). Results were similar in analyses of BMI-IR categories. CONCLUSIONS: People with normal weight and MetS or IR or with obesity but no MetS or IR were not uncommon in our sample. Risk factor clustering or IR appear to confer much of the risk for diabetes or CVD commonly associated with elevated BMI.     

Chronic kidney disease and cognitive decline in patients with type 2 diabetes at elevated cardiovascular risk

AimsWe addressed the question whether chronic kidney disease (CKD) may contribute to cognitive decline in type 2 diabetes.MethodsParticipants with type 2 diabetes with elevated cardiovascular risk or CKD from cognition substudies of two large trials were studied prospectively (CARMELINA: n = 2666, mean ± SD age 68.1 ± 8.7 years, CAROLINA: n = 4296; 64.7 ± 9.4 years). Estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) at baseline were related to cognitive performance (Mini-Mental State Examination (MMSE) and attention and executive functioning score (A&E)) in linear regression analyses, adjusted for demographics, cardiovascular risk factors and treatment, at baseline and follow-up.ResultsCKD at baseline was more common in CARMELINA than CAROLINA (eGFR<60 in 72.6 % and 19.6 %, macroalbuminuria in 35.0 % and 4.1 %, respectively). Baseline eGFR was related to A&E in CARMELINA (b = 0.02 per 10 ml/min/1.73m², 95%CI [0.01,0.03]). Baseline UACR was related to A&E in CAROLINA (b = ?0.01 per doubling of UACR mg/g, 95%CI [?0.02,?0.002]). Baseline UACR predicted decline in A&E in CAROLINA (median 6.1 years follow-up; b = ?0.01, 95%CI [?0.03,?0.0001] per doubling of UACR mg/g).ConclusionseGFR and UACR were associated with A&E in two cohorts with type 2 diabetes, enriched for CKD and cardiovascular disease. The small effect size estimates indicate limited impact of kidney dysfunction on cognition in this setting.ClinicalTrials.gov identifiersNCT01897532NCT01243424     

Nontraditional risk factors for cardiovascular disease in diabetes

People with type 2 diabetes are disproportionately affected by cardiovascular disease (CVD), compared with those without diabetes. Traditional risk factors do not fully explain this excess risk, and other "nontraditional" risk factors may be important. This review will highlight the importance of nontraditional risk factors for CVD in the setting of type 2 diabetes and discuss their role in the pathogenesis of the excess CVD morbidity and mortality in these patients. We will also discuss the impact of various therapies used in patients with diabetes on nontraditional risk factors.     

Non-traditional cardiovascular risk factors contribute to peripheral arterial disease in patients with type 2 diabetes

OBJECTIVE: This study evaluated the prevalence of peripheral arterial disease (PAD) in type 2 diabetes and its association with traditional and non-traditional cardiovascular (CV) risk factors. SUBJECTS AND METHODS: In 1610 type 2 diabetics PAD was defined as ankle-brachial pressure index (ABPI)<0.9. RESULTS: PAD prevalence was 17%, increased with age, diabetes duration, HbA 1c levels, previous CV events. There were no significant differences in the prevalence of traditional CV risk factors between patients with and without PAD. PAD patients had higher levels of fibrinogen (10.88+/-2.32 versus 10.2+/-2.23micromol/L; p<0.0001), uric acid (327.1+/-89.2 versus 315.2+/-83.3micromol/L, p<0.01), pulse pressure (70+/-18 versus 60+/-16mm Hg, p<0.0001), higher rate of microalbuminuria (21.3% versus 13.7%; p<0.05) and lower glomerular filtration rate (GFR, 80.7+/-24 versus 89.9+/-22 ml/min/1.73 m2; p<0.001) than those without. In age-gender-adjusted analysis, smoking (OR 1.5; CI: 1.07-2.2), HbA 1c (OR 1.45; CI: 1.07-2.08), high pulse pressure (OR 2.81; CI: 1.63-4.82), reduced GFR (OR 2.16; CI: 1.4-3.3), microalbuminuria (OR 1.62; CI: 1.11-2.36), high fibrinogen levels (OR 2.03; CI: 1.34-3.07) were associated with PAD. In multivariate analysis age, male sex, smoking, high pulse pressure, low GFR, high fibrinogen levels, previous CV events were independent risk factors for PAD. CONCLUSIONS: PAD prevalence is high in Type 2 diabetic patients. Non-traditional cardiovascular risk factors may be involved in the development of this complication.     

Increased risk of cardiovascular disease in newly diagnosed type 2 diabetic patients in a primary health care center in Trinidad

The prevalence of cardiovascular diseases (CVD) has increased sharply in the developing countries and because Type 2 diabetic patients are at increased risk for CVD, we assessed CVD risk factors in newly diagnosed Type 2 diabetic patients presenting in a primary health care center in Trinidad. Fasting and 2 h postprandial blood samples were collected from 387 (269 females, 118 males) newly diagnosed Type 2 diabetic patients (mean age: 53.1+/-6.6 years) for the determination of plasma glucose, creatinine, cholesterol (chol), triglyceride (TG) and % glycated hemoglobin (HbA(1c)) concentrations. Blood pressure and anthropometric indices were also measured. There were high prevalence rates of obesity (37%), overweight (35%), hypertension (21%), hypercholesterolemia (25%) and hypertriglyceridemia (22.3%) among the patients and these were significantly higher in women than men (P<0.001). Patients of Indian descent had a significantly higher prevalence of diastolic hypertension and hypertriglyceridemia compared with patients of African origin or mixed race (P<0.001). In comparison with males, female diabetic patients were at greater risk of cardiovascular morbidity and mortality. Early detection of CVD risk factors and treatment, particularly in women, may be beneficial management strategy in all local diabetic clinics in Trinidad.