-
1.
Neutrophil extracellular traps: The core player in vascular complications of diabetes mellitus.
Berezin, A
Diabetes & metabolic syndrome. 2019;(5):3017-3023
Abstract
Diabetes mellitus (DM) is the most important metabolic disease with major threat for public health and increased risk of premature death. The prevalence of DM steadily rises in developing and developed countries achieving the epidemic level. Manifestation and progression of DM corresponds to developing vasculopathies, such as retinopathy, micro- and macro angiopathies, which negatively influence on clinical outcomes and quality-of-life. Although there are remarkable differences in the prevalence of vasculopathy in various types of DM, hyperglycemia and lipotoxicity are discussed as a major factors contributing to vascular complications partly through inducing neutrophil extracellular trap (NET). The NET or NETosis is unique form of cell death, which is an important core component of innate immune system. The review is dedicated the role of NET as a link between endothelium, inflammation and thrombosis that is crucial for development of DM-induced vasculopathy. It has suggested that NET formation could be not just a target for the DM care, but also a biomarker for stratification of DM patients at higher risk of vascular complications.
-
2.
Effect of selective BET protein inhibitor apabetalone on cardiovascular outcomes in patients with acute coronary syndrome and diabetes: Rationale, design, and baseline characteristics of the BETonMACE trial.
Ray, KK, Nicholls, SJ, Ginsberg, HD, Johansson, JO, Kalantar-Zadeh, K, Kulikowski, E, Toth, PP, Wong, N, Cummings, JL, Sweeney, M, et al
American heart journal. 2019;:72-83
-
-
Free full text
-
Abstract
After an acute coronary syndrome (ACS), patients with diabetes remain at high risk for additional cardiovascular events despite use of current therapies. Bromodomain and extra-terminal (BET) proteins are epigenetic modulators of inflammation, thrombogenesis, and lipoprotein metabolism implicated in atherothrombosis. The BETonMACE trial tests the hypothesis that treatment with apabetalone, a selective BET protein inhibitor, will improve cardiovascular outcomes in patients with diabetes after an ACS. DESIGN Patients (n = 2425) with ACS in the preceding 7 to 90 days, with type 2 diabetes and low HDL cholesterol (≤40 mg/dl for men, ≤45 mg/dl for women), receiving intensive or maximum-tolerated therapy with atorvastatin or rosuvastatin, were assigned in double-blind fashion to receive apabetalone 100 mg orally twice daily or matching placebo. Baseline characteristics include female sex (25%), myocardial infarction as index ACS event (74%), coronary revascularization for index ACS (80%), treatment with dual anti-platelet therapy (87%) and renin-angiotensin system inhibitors (91%), median LDL cholesterol 65 mg per deciliter, and median HbA1c 7.3%. The primary efficacy measure is time to first occurrence of cardiovascular death, non-fatal myocardial infarction, or stroke. Assumptions include a primary event rate of 7% per annum in the placebo group and median follow-up of 1.5 years. Patients will be followed until at least 250 primary endpoint events have occurred, providing 80% power to detect a 30% reduction in the primary endpoint with apabetalone. SUMMARY BETonMACE will determine whether the addition of the selective BET protein inhibitor apabetalone to contemporary standard of care for ACS reduces cardiovascular morbidity and mortality in patients with type 2 diabetes. Results are expected in 2019.
-
3.
Relations between subclinical disease markers and type 2 diabetes, metabolic syndrome, and incident cardiovascular disease: the Jackson Heart Study.
Xanthakis, V, Sung, JH, Samdarshi, TE, Hill, AN, Musani, SK, Sims, M, Ghraibeh, KA, Liebson, PR, Taylor, HA, Vasan, RS, et al
Diabetes care. 2015;(6):1082-8
-
-
Free full text
-
Abstract
OBJECTIVE The presence of subclinical disease measures has been directly associated with the development of cardiovascular disease (CVD) in whites. African Americans (AAs) in the U.S. are at higher risk of CVD compared with non-Hispanic whites; however, data on the prevalence of subclinical disease measures in AAs and their association to CVD remain unclear and may explain the higher CVD risk in this group. RESEARCH DESIGN AND METHODS We evaluated 4,416 participants attending the first examination of the Jackson Heart Study (mean age 54 years; 64% women) with available subclinical disease measures. RESULTS There were 1,155 participants (26%) with subclinical disease, defined as the presence of one or more of the following: peripheral arterial disease, left ventricular hypertrophy, microalbuminuria, high coronary artery calcium (CAC) score, and low left ventricular ejection fraction. In cross-sectional analyses using multivariable-adjusted logistic regression, participants with metabolic syndrome (MetS) or diabetes (DM) had higher odds of subclinical disease compared with those without MetS and DM (odds ratios 1.55 [95% CI 1.30-1.85] and 2.86 [95% CI 2.32-3.53], respectively). Furthermore, the presence of a high CAC score and left ventricular hypertrophy were directly associated with the incidence of CVD (265 events) in multivariable-adjusted Cox proportional hazards regression models (P < 0.05). In prospective analyses, having MetS or DM significantly increased the hazard of incident CVD, independent of the presence of subclinical disease (P < 0.001). CONCLUSIONS In our community-based sample of AAs, we observed a moderately high prevalence of subclinical disease, which in turn translated into a greater risk of CVD, especially in people with MetS and DM.
-
4.
Metabolic syndrome in young people.
Poyrazoglu, S, Bas, F, Darendeliler, F
Current opinion in endocrinology, diabetes, and obesity. 2014;(1):56-63
Abstract
PURPOSE OF REVIEW The prevalence of obesity is on the increase, and consequently metabolic syndrome is also becoming a serious health problem in children and adolescents all over the world. This review attempts to summarize the recent literature on metabolic syndrome in children and adolescents. RECENT FINDINGS To date, a standard definition of metabolic syndrome for the pediatric population is not available. Recently, the International Diabetes Federation has proposed a new set of criteria to define metabolic syndrome in children and adolescents aged 6-16 years. The relationships between obesity, insulin resistance and metabolic syndrome may be explained by the pattern of lipid partitioning. Fatty liver plays a central role in the insulin-resistant state in obese adolescents. Although insulin resistance has been proposed as the central factor leading to the abnormalities observed in metabolic syndrome, most definitions of metabolic syndrome use impaired fasting glucose as a marker. Nutrition impairment during both prenatal and early postnatal life can cause metabolic disturbances leading to insulin-resistance, type 2 diabetes, hypertension and cardiovascular disease. SUMMARY Metabolic syndrome prevalence in children and adolescents is on the increase. Therefore, the emphasis in all studies and programs related to metabolic syndrome should be focused on prevention, early detection of metabolic risk factors and interventions that will have a significant impact on future adult health.
-
5.
The effect of excess weight gain with intensive diabetes mellitus treatment on cardiovascular disease risk factors and atherosclerosis in type 1 diabetes mellitus: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) study.
Purnell, JQ, Zinman, B, Brunzell, JD, ,
Circulation. 2013;(2):180-7
-
-
Free full text
-
Abstract
BACKGROUND Intensive diabetes mellitus therapy of type 1 diabetes mellitus reduces diabetes mellitus complications but can be associated with excess weight gain, central obesity, and dyslipidemia. The purpose of this study was to determine whether excessive weight gain with diabetes mellitus therapy of type 1 diabetes mellitus is prospectively associated with atherosclerotic disease. METHODS AND RESULTS Subjects with type 1 diabetes mellitus (97% white, 45% female, mean age 35 years) randomly assigned to intensive or conventional diabetes mellitus treatment during the Diabetes Control and Complications Trial (DCCT) underwent intima-media thickness (n = 1015) and coronary artery calcium score (n = 925) measurements during follow-up in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. Intensive treatment subjects were classified by quartile of body mass index change during the DCCT. Excess gainers (4th quartile, including conventional treatment subjects meeting this threshold) maintained greater body mass index and waist circumference, needed more insulin, had greater intima-media thickness (+5%, P < 0.001 EDIC year 1, P = 0.003 EDIC year 6), and trended toward greater coronary artery calcium scores (odds ratio, 1.55; confidence interval, 0.97 to 2.49; P = 0.07) than minimal gainers. DCCT subjects meeting metabolic syndrome criteria for waist circumference and blood pressure had greater intima-media thickness in both EDIC years (P = 0.02 to < 0.001); those meeting high-density lipoprotein criteria had greater coronary artery calcium scores (odds ratio, 1.6; confidence interval, 1.1 to 2.4; P = 0.01) during follow-up. Increasing frequency of a family history of diabetes mellitus, hypertension, and hyperlipidemia was associated with greater intima-media thickness with intensive but not conventional treatment. CONCLUSIONS Excess weight gain in DCCT is associated with sustained increases in central obesity, insulin resistance, dyslipidemia and blood pressure, as well as more extensive atherosclerosis during EDIC. CLINICAL TRIAL REGISTRATION URL for DCCT http://clinicaltrials.gov; Unique identifier: NCT00360815. URL for EDIC http://clinicaltrials.gov; Unique identifier: NCT00360893.
-
6.
[Nonalcoholic fatty liver disease as a risk factor of macroangiopahty in patients with type 2 diabetes].
Trojak, A, Idzior-Waluś, B
Przeglad lekarski. 2012;(12):1276-9
Abstract
Nonalcoholic fatty liver disease (NAFLD) is recognized in 20-30% of general population but among the people with impaired glucose metabolism is about 70-90%. There is increasing number publications that show strong association between NAFLD, metabolic syndrome and insulin resistance as risk factors of cardiovascular complication. Gens PNPLAL3 NCAN, LYPAL1 and GCKR that have been linked to lipid metabolism disorders or impaired glucose metabolism can also contribute to development of NAFLD. The reduction of body mass and of known risk factors of atherosclerosis and restriction of simple carbohydrates in diet contribute to regression of NAFLD.
-
7.
[General concept and pathophysiological mechanisms of progression of macrovascular complications in diabetes].
Kashiwagi, A
Nihon rinsho. Japanese journal of clinical medicine. 2010;(5):777-87
Abstract
Macrovascular complications in diabetes consist of 2 basic pathophysiological characteristics such as obstructive atherosclerotic lesions and non-obstructive sclerotic arterial lesions. The patients with former lesions are frequently complicated with postprandial hyperglycemia, insulin resistance, hyperinsulinemia, metabolic syndrome, smoking or high LDL-C concentrations. The latter lesions are usually characterized by diffuse, multi-vessel diseases and typically found in patients with long duration of diabetes and advanced diabetic retinopathy as well as nephropathy. Cardiovascular events or death in diabetes are as equally high as non-diabetic patients with a previous history of ischemic coronary artery diseases in not only Finish study but also Japanese J-ACCES study. It is now very clear that the progression of macrovascular complications in diabetes can be efficiently prevented by a strict multifactorial control of all coronary risk factors including hyperglycemia.
-
8.
In support of an early polypharmacy approach to the treatment of type 2 diabetes.
Wright, EE, Stonehouse, AH, Cuddihy, RM
Diabetes, obesity & metabolism. 2010;(11):929-40
Abstract
Type 2 diabetes (T2DM) is a multifaceted disease, characterized by hyperglycaemia, resulting from a combination of insulin resistance, impaired incretin action and β-cell dysfunction leading to relative insulin deficiency. Although traditional anti-diabetes agents improve hyperglycaemia, they do so at a cost, which may entail hypoglycemia and increased body weight; exacerbating dyslipidemia, hypertension and components of insulin resistance and metabolic syndrome associated with T2DM-potentially increasing cardiovascular risk. At diagnosis, many patients with T2DM are treated with medical nutritional therapy (MNT) and exercise, then single or multiple oral anti-diabetes agents until treatment failure, when insulin is used. This strategy has been challenged by recommendations for polypharmacy approaches to the treatment of T2DM, as current strategies are unable to improve multiple aspects of the disease, nor are they likely to address underlying pathophysiology. Although the 2009 American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) treatment algorithm recommends a stepwise approach with MNT and metformin, later adding oral agents, incretin-based therapies or insulin, some experts have recommended a more aggressive approach. In his 2008 ADA Banting Lecture, Dr. Ralph DeFronzo recommended early treatment with metformin, TZD and exenatide at initiation of therapy. The authors' of this article recommend an aggressive early polypharmacy approach addressing underlying pathophysiology, including the incretin defect-with MNT and exercise, metformin and an incretin-based therapy and/or basal insulin if glycemic goal is not achieved within 3 months. This approach attempts to modify the disease, aiming for tight glycemic control, weight loss, reduced hypoglycemia, improvements to hypertension, dyslipidemia and insulin resistance-and improved cardiovascular outcomes.
-
9.
Clinical insights from the Fenofibrate Intervention and Event Lowering in Diabetes study: a community practice perspective.
Toth, PP
International journal of clinical practice. 2009;(6):903-11
Abstract
Achieving adequate control of cardiovascular risk in type 2 diabetes mellitus (DM) is crucially important; however, the atherogenic dyslipidaemia (including low high-density lipoprotein cholesterol and hypertriglyceridaemia) typically encountered in type 2 DM is often managed inadequately. Evidence from the Fenofibrate Intervention and Event Lowering in Diabetes study suggests that fenofibrate reduces the risk of long-term macrovascular and microvascular type 2 diabetic complications, especially in patients demonstrating features of the metabolic syndrome. Fenofibrate represents a useful treatment option for controlling cardiovascular risk in type 2 diabetes patients in the community setting.
-
10.
How can we improve the management of vascular risk in type 2 diabetes: insights from FIELD.
Steiner, G
Cardiovascular drugs and therapy. 2009;(5):403-8
Abstract
PURPOSE Intensive multifactorial risk factor intervention, targeting blood glucose, blood pressure and low-density lipoprotein cholesterol, is central to therapeutic management of type 2 diabetes. This strategy reduces, but does not eliminate the risk for cardiovascular complications, and microvascular complications such as diabetic retinopathy and nephropathy still continue to develop or progress. Fibrates have been shown to be effective in managing mixed dyslipidemia characterized by elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C), typically associated with type 2 diabetes. METHODS Data were reviewed from the largest fibrate study to date, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study which evaluated the effect of fenofibrate treatment in 9,795 patients with type 2 diabetes (about 80% without prior cardiovascular disease or microvascular complications). RESULTS Although FIELD did not show a significant benefit with fenofibrate for major coronary events (the primary outcome), there was significant reduction in total cardiovascular events (relative risk reduction [RRR] 11%, p = 0.035 vs. placebo). The clinical benefits of fenofibrate treatment were greater in patients with marked mixed dyslipidemia (elevated triglycerides >or=200 mg/dL and low plasma levels of HDL-C), features of the metabolic syndrome commonly observed in patients with type 2 diabetes, with a RRR of 27%, p = 0.005. These data are consistent with evidence from other fibrate trials showing increased treatment benefits in patients with metabolic syndrome or type 2 diabetes and mixed dyslipidemia. The FIELD study also provided promising data for microvascular benefits with fenofibrate, specifically on the need for laser treatment for diabetic retinopathy, progression of albuminuria, and prevention of diabetes-related lower-limb amputation. CONCLUSIONS Adding fenofibrate to primary statin therapy might be a useful strategy to address residual macrovascular and microvascular risk in type 2 diabetes.