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Cardiovascular Diabetology Apr 2018Cardiovascular disease (CVD) is the leading cause of mortality in people with type 2 diabetes mellitus (T2DM), yet a significant proportion of the disease burden cannot... (Review)
Review
Cardiovascular disease (CVD) is the leading cause of mortality in people with type 2 diabetes mellitus (T2DM), yet a significant proportion of the disease burden cannot be accounted for by conventional cardiovascular risk factors. Hypertension occurs in majority of people with T2DM, which is substantially more frequent than would be anticipated based on general population samples. The impact of hypertension is considerably higher in people with diabetes than it is in the general population, suggesting either an increased sensitivity to its effect or a confounding underlying aetiopathogenic mechanism of hypertension associated with CVD within diabetes. In this contribution, we aim to review the changes observed in the vascular tree in people with T2DM compared to the general population, the effects of established anti-diabetes drugs on microvascular outcomes, and explore the hypotheses to account for common causalities of the increased prevalence of CVD and hypertension in people with T2DM.
Topics: Animals; Cardiovascular System; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Hypertension; Hypoglycemic Agents; Microcirculation; Prevalence; Risk Factors; Treatment Outcome
PubMed: 29669543
DOI: 10.1186/s12933-018-0703-2 -
The American Journal of Medicine Jun 2017Epidemiologic and clinical data from the last 2 decades have shown that the prevalence of heart failure in diabetes is very high, and the prognosis for patients with... (Review)
Review
Epidemiologic and clinical data from the last 2 decades have shown that the prevalence of heart failure in diabetes is very high, and the prognosis for patients with heart failure is worse in those with diabetes than in those without diabetes. Experimental data suggest that various mechanisms contribute to the impairment in systolic and diastolic function in patients with diabetes, and there is an increased recognition that these patients develop heart failure independent of the presence of coronary artery disease or its associated risk factors. In addition, current clinical data demonstrated that treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin reduced hospitalization for heart failure in patients with type 2 diabetes mellitus and high cardiovascular risk. This review article summarizes recent data on the prevalence, prognosis, pathophysiology, and therapeutic strategies to treat patients with diabetes and heart failure.
Topics: Benzhydryl Compounds; Comorbidity; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Glucosides; Heart Failure; Humans; Hypoglycemic Agents; Incidence; Prevalence; Prognosis
PubMed: 28526183
DOI: 10.1016/j.amjmed.2017.04.010 -
Vascular Pharmacology Mar 2017Diabetic microangiopathy, including retinopathy, is characterized by abnormal growth and leakage of small blood vessels, resulting in local edema and functional... (Review)
Review
Diabetic microangiopathy, including retinopathy, is characterized by abnormal growth and leakage of small blood vessels, resulting in local edema and functional impairment of the depending tissues. Mechanisms leading to the impairment of microcirculation in diabetes are multiple and still largely unclear. However, a dysregulated vascular regeneration appears to play a key role. In addition, oxidative and hyperosmolar stress, as well as the activation of inflammatory pathways triggered by advanced glycation end-products and toll-like receptors, have been recognized as key underlying events Here, we review recent knowledge on cellular and molecular pathways of microvascular disease in diabetes. We also highlight how new insights into pathogenic mechanisms of vascular damage in diabetes may indicate new targets for prevention and treatment.
Topics: Animals; Capillary Permeability; Diabetic Angiopathies; Glycation End Products, Advanced; Humans; Inflammation Mediators; Microcirculation; Microvessels; Neovascularization, Pathologic; Oxidative Stress; Prognosis; Signal Transduction; Toll-Like Receptors
PubMed: 28137665
DOI: 10.1016/j.vph.2017.01.004 -
Arteriosclerosis, Thrombosis, and... Jun 2016
Review
Topics: Animals; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Endothelial Cells; Humans; Inflammation; Lipoproteins; Risk Factors
PubMed: 27225786
DOI: 10.1161/ATVBAHA.116.307302 -
Cardiovascular Diabetology May 2018Exercise training is considered a cornerstone in the management of type 2 diabetes, which is associated with impaired endothelial function. However, the association of... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Exercise training is considered a cornerstone in the management of type 2 diabetes, which is associated with impaired endothelial function. However, the association of exercise training with endothelial function in type 2 diabetes patients has not been fully understood. This meta-analysis aimed to investigate their associations with focus on exercise types.
METHODS
Databases were searched up to January 2018 for studies evaluating the influences of exercise training with durations ≥ 8 weeks on endothelial function assessed by flow-mediated dilation (FMD) among type 2 diabetes patients or between type 2 diabetics and non-diabetics. Data were pooled using random-effects models to obtain the weighted mean differences (WMDs) and 95% confidence intervals (CIs).
RESULTS
Sixteen databases were included. Exercise training resulted in an overall improvement in FMD by 1.77% (95% CI 0.94-2.59%) in type 2 diabetes patients. Specifically, both aerobic and combined aerobic and resistance exercise increased FMD by 1.21% (95% CI 0.23-2.19%) and 2.49% (95% CI 1.17-3.81%), respectively; but resistance exercise only showed a trend. High-intensity interval aerobic exercise did not significantly improve FMD over moderate-intensity continuous exercise. Notably, the improvement in FMD among type 2 diabetes patients was smaller compared with non-diabetics in response to exercise training (WMD - 0.72%, 95% CI - 1.36 to - 0.08%) or specifically to aerobic exercise (WMD - 0.65%, 95% CI - 1.31 to 0.01%).
CONCLUSIONS
Exercise training, in particular aerobic and combined exercise, improves endothelial function in type 2 diabetes patients, but such an improvement appears to be weakened compared with non-diabetics. Trial registration PROSPERO CRD42018087376.
Topics: Aged; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Exercise Therapy; Exercise Tolerance; Female; Humans; Male; Middle Aged; Recovery of Function; Treatment Outcome; Vasodilation
PubMed: 29720185
DOI: 10.1186/s12933-018-0711-2 -
BMC Endocrine Disorders Feb 2021Advanced glycation end-products (AGEs) are heterogeneous molecules produced by the non-enzymatic glycation of proteins, lipids, or nucleic acids during hyperglycaemia.... (Review)
Review
Advanced glycation end-products (AGEs) are heterogeneous molecules produced by the non-enzymatic glycation of proteins, lipids, or nucleic acids during hyperglycaemia. Accumulation of AGEs in the peripheral nerves has recently been proposed as an additional risk factor for the development of diabetic neuropathy (DN). The gold standard for measurement of tissue-bound AGEs is tissue biopsy. However, their assessment with the newer, fast and simple method of skin autofluorescence (sAF) has recently gained special interest by virtue of its non-invasive, highly reproducible nature and its acceptable correlation with the reference method of skin biopsy. Accumulation of tissue AGEs evaluated by sAF has been shown to independently correlate with DN. Importantly, increasing evidence underscores their potential value as early biomarkers of the latter. Further important associations include diabetic nephropathy, diabetic retinopathy and cardiovascular autonomic neuropathy. However, the value of the implementation of screening with skin AGEs for DN remains unclear. The aim of the present review is to critically summarise current evidence on the association between skin AGEs and diabetic microvascular complications, with a particular emphasis on diabetic neuropathy, and to note the most important limitations of existing knowledge. Longer follow-up studies are also highly anticipated to clarify its role and provide data on patient selection and cost-effectiveness.
Topics: Diabetic Angiopathies; Diabetic Neuropathies; Glycation End Products, Advanced; Humans; Optical Imaging; Skin
PubMed: 33622304
DOI: 10.1186/s12902-021-00697-7 -
Clinical Epigenetics Feb 2020The vasculature not only transports oxygenated blood, metabolites, and waste products but also serves as a conduit for hormonal communication between distant tissues.... (Review)
Review
The vasculature not only transports oxygenated blood, metabolites, and waste products but also serves as a conduit for hormonal communication between distant tissues. Therefore, it is important to maintain homeostasis within the vasculature. Recent studies have greatly expanded our understanding of the regulation of vasculature development and vascular-related diseases at the epigenetic level, including by protein posttranslational modifications, DNA methylation, and noncoding RNAs. Integrating epigenetic mechanisms into the pathophysiologic conceptualization of complex and multifactorial vascular-related diseases may provide promising therapeutic approaches. Several reviews have presented detailed discussions of epigenetic mechanisms not including histone methylation in vascular biology. In this review, we primarily discuss histone methylation in vascular development and maturity, and in vascular diseases.
Topics: Aortic Dissection; Animals; Aorta, Thoracic; Aortic Aneurysm; Atherosclerosis; Blood Vessels; Diabetic Angiopathies; Endothelium, Vascular; Histones; Humans; Methylation; Mice; Neovascularization, Pathologic; Pulmonary Arterial Hypertension; Vascular Diseases
PubMed: 32070413
DOI: 10.1186/s13148-020-00826-4 -
International Journal of Molecular... May 2022Late vascular complications play a prominent role in the diabetes-induced increase in morbidity and mortality. Diabetes mellitus is recognised as a risk factor driving... (Review)
Review
Late vascular complications play a prominent role in the diabetes-induced increase in morbidity and mortality. Diabetes mellitus is recognised as a risk factor driving atherosclerosis and cardiovascular mortality; even after the normalisation of blood glucose concentration, the event risk is amplified-an effect called "glycolytic memory". The hallmark of this glycolytic memory and diabetic pathology are advanced glycation end products (AGEs) and reactive glucose metabolites such as methylglyoxal (MGO), a highly reactive dicarbonyl compound derived mainly from glycolysis. MGO and AGEs have an impact on vascular and organ structure and function, contributing to organ damage. As MGO is not only associated with hyperglycaemia in diabetes but also with other risk factors for diabetic vascular complications such as obesity, dyslipidaemia and hypertension, MGO is identified as a major player in the development of vascular complications in diabetes both on micro- as well as macrovascular level. In diabetes mellitus, the detoxifying system for MGO, the glyoxalase system, is diminished, accounting for the increased MGO concentration and glycotoxic load. This overview will summarise current knowledge on the effect of MGO and AGEs on vascular function.
Topics: Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Glycation End Products, Advanced; Humans; Hyperglycemia; Magnesium Oxide; Pyruvaldehyde
PubMed: 35682865
DOI: 10.3390/ijms23116186 -
Journal of Diabetes Research 2016
Topics: Animals; Cardiovascular Diseases; Diabetic Angiopathies; Endothelial Progenitor Cells; Endothelium, Vascular; Humans; Hypoglycemic Agents; Neovascularization, Pathologic
PubMed: 26989698
DOI: 10.1155/2016/5349801 -
Frontiers in Endocrinology 2022Type 2 diabetes mellitus (T2DM) causes peripheral vascular disease because of which several blood-borne factors, including vital nutrients fail to reach the affected... (Review)
Review
Type 2 diabetes mellitus (T2DM) causes peripheral vascular disease because of which several blood-borne factors, including vital nutrients fail to reach the affected tissue. Tissue epigenome is sensitive to chronic hyperglycemia and is known to cause pathogenesis of micro- and macrovascular complications. These vascular complications of T2DM may perpetuate the onset of organ dysfunction. The burden of diabetes is primarily because of a wide range of complications of which nonhealing diabetic ulcers represent a major component. Thus, it is imperative that current research help recognize more effective methods for the diagnosis and management of early vascular injuries. This review addresses the significance of epigenetic processes such as DNA methylation and histone modifications in the evolution of macrovascular and microvascular complications of T2DM.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Epigenesis, Genetic; DNA Methylation; Vascular Diseases
PubMed: 36568089
DOI: 10.3389/fendo.2022.989844