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Adverse pregnancy outcomes in women with diabetes-related microvascular disease and risks of disease progression in pregnancy: A systematic review and meta-analysis.
Relph, S, Patel, T, Delaney, L, Sobhy, S, Thangaratinam, S
PLoS medicine. 2021;(11):e1003856
Abstract
BACKGROUND The rise in the global prevalence of diabetes, particularly among younger people, has led to an increase in the number of pregnant women with preexisting diabetes, many of whom have diabetes-related microvascular complications. We aimed to estimate the magnitude of the risks of adverse pregnancy outcomes or disease progression in this population. METHODS AND FINDINGS We undertook a systematic review and meta-analysis on maternal and perinatal complications in women with type 1 or 2 diabetic microvascular disease and the risk factors for worsening of microvascular disease in pregnancy using a prospective protocol (PROSPERO CRD42017076647). We searched major databases (January 1990 to July 2021) for relevant cohort studies. Study quality was assessed using the Newcastle-Ottawa Scale. We summarized the findings as odds ratios (ORs) with 95% confidence intervals (CIs) using random effects meta-analysis. We included 56 cohort studies involving 12,819 pregnant women with diabetes; including 40 from Europe and 9 from North America. Pregnant women with diabetic nephropathy were at greater risk of preeclampsia (OR 10.76, CI 6.43 to 17.99, p < 0.001), early (<34 weeks) (OR 6.90, 95% CI 3.38 to 14.06, p < 0.001) and any preterm birth (OR 4.48, CI 3.40 to 5.92, p < 0.001), and cesarean section (OR 3.04, CI 1.24 to 7.47, p = 0.015); their babies were at higher risk of perinatal death (OR 2.26, CI 1.07 to 4.75, p = 0.032), congenital abnormality (OR 2.71, CI 1.58 to 4.66, p < 0.001), small for gestational age (OR 16.89, CI 7.07 to 40.37, p < 0.001), and admission to neonatal unit (OR 2.59, CI 1.72 to 3.90, p < 0.001) compared to those without nephropathy. Diabetic retinopathy was associated with any preterm birth (OR 1.67, CI 1.27 to 2.20, p < 0.001) and preeclampsia (OR 2.20, CI 1.57 to 3.10, p < 0.001) but not other complications. The risks of onset or worsening of retinopathy were increased in women who were nulliparous (OR 1.75, 95% CI 1.28 to 2.40, p < 0.001), smokers (OR 2.31, 95% CI 1.25 to 4.27, p = 0.008), with existing proliferative disease (OR 2.12, 95% CI 1.11 to 4.04, p = 0.022), and longer duration of diabetes (weighted mean difference: 4.51 years, 95% CI 2.26 to 6.76, p < 0.001) compared to those without the risk factors. The main limitations of this analysis are the heterogeneity of definition of retinopathy and nephropathy and the inclusion of women both with type 1 and type 2 diabetes. CONCLUSIONS In pregnant women with diabetes, presence of nephropathy and/or retinopathy appear to further increase the risks of maternal complications.
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Nailfold capillaroscopy in common non-rheumatic conditions: A systematic review and applications for clinical practice.
Ciaffi, J, Ajasllari, N, Mancarella, L, Brusi, V, Meliconi, R, Ursini, F
Microvascular research. 2020;:104036
Abstract
OBJECTIVE The role of nailfold capillaroscopy (NC) in common non-rheumatic conditions has not been systematically reported. The aim of this review is to outline NC features observed in frequent non-rheumatic conditions, providing a practical tool to support rheumatologists for the interpretation of capillaroscopic abnormalities in patients with no established connective tissue disease (CTD). METHODS We undertook a systematic search in PubMed and Web of Science databases. Studies reporting adults or children with common non-rheumatic diseases or conditions in which quantitative and/or qualitative assessment of morphological nailbed capillary findings was obtained, were included. The presence of a control group composed by subjects not affected by the studied condition and direct comparison of findings between groups were needed. RESULTS We included 25 articles. Diabetes mellitus (11 studies), glaucoma (7 studies) and essential hypertension (3 studies) were the most represented diseases. Reduced capillary density, tortuosity, dilated capillaries, microhaemorrhages, ramified capillaries and avascular areas can be observed in diabetic patients. Association was reported between poor glycaemic control or longer duration of diabetes, or presence of microvascular complications as retinopathy and neuropathy, and more severe capillaroscopic abnormalities. Decreased capillary density, tortuosity, microhaemorrhages, dilated capillaries, avascular areas and ramifications might also be present in glaucoma, while in essential hypertension a reduced capillary density might be expected. CONCLUSION Abnormal capillaroscopic findings are not uncommon even in individuals with no CTD. Therefore, presence of comorbidities known to potentially affect the microvascular array should always be investigated in patients undergoing NC and the interpretation of findings might be weighted accordingly.
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Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and microvascular outcomes in patients with type 2 diabetes: systematic review and meta-analysis.
Dorsey-Treviño, EG, González-González, JG, Alvarez-Villalobos, N, González-Nava, V, Contreras-Garza, BM, Díaz González-Colmenero, A, Rodríguez-Tamez, G, Barrera-Flores, FJ, Farrell, AM, Montori, VM, et al
Journal of endocrinological investigation. 2020;(3):289-304
Abstract
PURPOSE The effect of the sodium-glucose 2 (SGLT-2) inhibitors on microvascular complications remains uncertain. We performed a systematic review to determine the efficacy of the SGLT-2 inhibitors on microvascular outcomes in patients with type 2 diabetes. METHODS A comprehensive search was performed using Ovid, MEDLINE, EMBASE, Web of Science, and Scopus from inception to May 2019. Randomized trials comparing SGLT-2 inhibitors with placebo or other medication for type 2 diabetes for ≥ 4 weeks were included. Diabetes-related microvascular complications such as nephropathy, retinopathy, neuropathy, and peripheral vascular disease were evaluated. A random-effect model using mean differences for continuous outcomes and risk ratio for dichotomous outcomes was used to synthesize data. PROSPERO (CRD 42017076460). RESULTS A total of 40 RCTs with overall moderate quality of evidence were included. SGLT-2 inhibitors reduced the risk of renal-replacement therapy (0.65; 95% CI 0.54-0.79), renal death (0.57; 95% CI 0.49-0.65), and progression of albuminuria (0.69; 95% CI 0.66-0.73). Conversely, they appeared ineffective in maintaining eGFR (0.33; 95% CI - 0.74 to 1.41) or reducing serum creatinine (- 0.07; 95% CI - 0.26 to 0.11), whereas urine albumin-creatinine ratio (- 23.4; 95% CI - 44.6 to - 2.2) was reduced. Risk of amputation was non-significant (1.30; 95% CI 0.93-1.83). No available data were found regarding neuropathy and retinopathy to perform a quantitative analysis. CONCLUSION SGLT-2 inhibitors may reduce the risk of renal patient-important outcomes but fail to improve surrogate outcomes. Apparently, no increased risk of amputations was observed with these medications. No data were available regarding other microvascular complications.
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SCUBE2, vascular endothelium, and vascular complications: A systematic review.
Ali, H
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2020;:110129
Abstract
The vascular endothelium plays a vital role in regulating normal vascular function. Endothelial lining maintains the balance of thrombolytic and fibrinolytic microenvironment in the vasculature. Alterations of vascular endothelium referred to as endothelial dysfunction, caused the pathological changes in vessel wall such activation of proinflammatory and procoagulatory that initiate atherosclerosis. The concept that endothelial dysfunction plays a critical role in the initiation of atherosclerosis due to vascular inflammation gained tremendous attention. Diabetes mellitus is a metabolic-related disease that caused high mortality and morbidity, leading to its cardiovascular complication over the past decade. Atherosclerosis is the leading cardiovascular complication in diabetes mellitus. Despite metabolic and glycemic control, atherosclerotic plaque progression remains an enormous problem in diabetes mellitus complications. Thus, new inroads therapeutic approach in preventing complications that induced inflammation in endothelial cells could help prevent the disease progression. Signal peptide-CUB-EGF like domain-containing protein 2 (SCUBE2) expressed in vascular endothelium and reported to involve in inflammation. A recent study reported an increased SCUBE2 expression in diabetes mellitus and correlated with high expression of endothelin-1 (ET-1), a proinflammatory endothelial cell-derived peptide. Moreover, this gene showed to increase during atherosclerosis development. The present systematic review will summarize the involvement of SCUBE2 in vascular endothelium function changes and vascular complication, particularly in diabetes mellitus and atherosclerosis.
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Minireview: The Introduction of COVID-19 and Microvascular Disease-Introduction of COVID-19 and the Relationship between Its Receptor and Diabetic Vascular Complications.
Song, Y, Ma, Q, Lin, P, Qin, D, Lu, D, Fan, X
Critical reviews in eukaryotic gene expression. 2020;(6):499-508
Abstract
In December of 2019, a novel coronavirus, which is SARS-CoV-2, broke out in the world and caused tremendous human and financial losses. According to a descriptive study by the relative hospital about the epidemiological and clinical features of 52 critically ill patients, the expert panel found that people with cardiovascular disease and diabetes comprise a large proportion of the patients with chronic disease. In this review, we discuss the structural biology of the SARS-CoV-2 in combination with the characteristics of its binding protein, ACE2, which is an important receptor in the cardiovascular system and may have potential relationships with various diabetic diseases. We hope we can provide useful recommendations for patients with diabetes after becoming infected by the virus or provide directions to doctors on treatment options.
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Vitamin D supplementation in the treatment of type 2 diabetic microangiopathy: A protocol for a systematic review and meta-analysis.
Chen, J, Gong, X, Liu, J, Wang, T, Shi, X, Zhang, X, Chen, Q
Medicine. 2020;(33):e20978
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Abstract
BACKGROUND The number of people with diabetes is growing exponentially.Human studies have shown that vitamin D supplementation is beneficial for type 2 diabetic microangiopathy. However, owing to the low quality, small sample size, and methodological heterogeneity of these studies, this conclusion is not convincing. Consequently, in order to determine whether vitamin D supplementation is effective and safe in type 2 diabetic microangiopathy, it is necessary to conduct a meta-analysis of high-quality clinical trials. METHODS We will search each database from the built-in until March 2020. The English literature mainly searches Cochrane Library, PubMed, EMBASE, and Web of Science, while the Chinese literature comes from CNKI, CBM, VIP, and Wangfang database. Simultaneously we will retrieval clinical registration tests and grey literatures. In this study, only the clinical randomized controlled trials were selected to evaluate the efficacy and safety of vitamin D in the treatment of type 2 diabetic microangiopathy. The two researchers independently conducted literature selection, data extraction and quality assessment. Statistical heterogeneity among studies will be evaluated using the Cochran Q test (x) and the I statistical value. We will utilize the Review Manage software V5.3.0 (The Nordic Cochrane Center, The Cochrane Collaboration, 2014, Copenhagen, Denmark) to statistically analyze all data. ETHICS AND DISSEMINATION Ethics and dissemination: This study is a systematic review of vitamin D supplementation as a treatment of type 2 diabetic microangiopathy. RESULTS This study will provide high-quality synthesis of effectiveness and safety of vitamin D supplementation for type 2 diabetic microangiopathy. CONCLUSION This systematic review aims to provide new options for vitamin D treatment of type 2 diabetic microangiopathy in terms of its efficacy and safety. REGISTRATION NUMBER LNPLASY202050055.
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Primary versus secondary cardiorenal prevention in type 2 diabetes: Which newer anti-hyperglycaemic drug matters?
Giugliano, D, Ceriello, A, De Nicola, L, Perrone-Filardi, P, Cosentino, F, Esposito, K
Diabetes, obesity & metabolism. 2020;(2):149-157
Abstract
We are observing a resurgence of major diabetic vascular complications after a period of dramatic decrease during the period 1990 to 2010. The classical division of cardiovascular prevention into primary (with an event) and secondary (without an event) is largely used to describe cardiovascular risk in type 2 diabetes (T2D); however, there is evidence that the cardiovascular risk in diabetes may range from highest in patients who experienced a previous cardiovascular event to mild in patients with the main risk factors at target. Herein, we present details of the 14 cardiovascular outcome trials (CVOTs) published to date, including the total population investigated, and their separation into primary (T2D + multiple risk factors) and secondary prevention (T2D + established cardiovascular disease [CVD]) populations as detailed within the trials. We also summarize evidence for the effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium glucose co-transporter-2 inhibitors (SGLT-2i) versus placebo on the risk of major cardiovascular events (MACE), heart failure (HF) and diabetic kidney disease (DKD). In primary prevention, SGLT-2i reduce both the risk of hospitalization for HF and progression of DKD; in secondary prevention, SGLT-2i are effective on the three endpoints, DPP-4i are neutral, while GLP1-RA show mixed results.
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Lipid management for cardiovascular risk reduction in type 1 diabetes.
Tell, S, Nadeau, KJ, Eckel, RH
Current opinion in endocrinology, diabetes, and obesity. 2020;(4):207-214
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PURPOSE OF REVIEW To review the recent evidence for lipid management in type 1 diabetes (T1D) for cardiovascular risk reduction. RECENT FINDINGS Individuals with T1D are at increased risk for cardiovascular morbidity and mortality, with atherosclerosis beginning as early as adolescence. Elevated low-density lipoprotein cholesterol (LDL-C), triglycerides, and lipoprotein (a) are associated with increased cardiovascular risk in T1D. Although high-density lipoprotein cholesterol (HDL-C) in T1D is often normal or higher than in nondiabetic controls, HDL in T1D has structural alterations, which make it proatherogenic rather than cardioprotective. Similarly, although LDL-C is not particularly elevated in T1D, LDL still contributes to cardiovascular risk. Studies in individuals with diabetes have primarily included T2D participants, with a much smaller number of T1D participants; such studies have shown that lipid-lowering therapies, such as statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce LDL-C levels and cardiovascular events in both those with and without diabetes. Individuals with T1D have increased cholesterol absorption, suggesting that ezetimibe may be particularly effective in T1D. Results of the REDUCE-IT trial show cardiovascular risk reduction from high-dose omega-3 fatty acid (Icosapent Ethyl) therapy in patients with diabetes (primarily type 2 diabetes), independent of triglyceride lowering, but similar data in T1D are currently lacking. SUMMARY Individuals with T1D are at high risk of cardiovascular disease, necessitating close lipid monitoring and management from adolescence through adulthood.
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Managing Diabetes and Preventing Heart Disease: Have We Found a Safe and Effective Agent?
Cheng, JWM, Colucci, VJ, Kalus, JS, Spinler, SA
The Annals of pharmacotherapy. 2019;(5):510-522
Abstract
OBJECTIVE While improving glycemic control with antihyperglycemics has been demonstrated to reduce microvascular complications, the benefits of reduction in cardiovascular diseases (CVDs) have not been demonstrated with older agents. This article reviews current evidence of the CV outcomes of newer antihyperglycemics approved since 2008. DATA SOURCES Peer-reviewed articles were identified from MEDLINE (1966 to October 31, 2018) using search terms exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide, alogliptin, linagliptin, saxagliptin, sitagliptin, canagliflozin, dapagliflozin, empagliflozin, mortality, myocardial infarction (MI), heart failure (HF), and stroke. STUDY SELECTION AND DATA EXTRACTION A total of 12 pertinent double-blinded randomized controlled trials were included. DATA SYNTHESIS Liraglutide, empagliflozin, and canagliflozin have been shown in patients with CV diseases and high risk of developing CV disease to be superior to placebo in improving CV outcomes. Saxagliptin and alogliptin have both been demonstrated to increase HF hospitalization, whereas sitagliptin has not. Relevance to Patient Care and Clinical Practice: In contrast to older-generation antihyperglycemics, selected new antihyperglycemic agents have been shown to be superior to placebo in improving CV outcomes. Clinicians may now be able to provide high-risk patients agents that not only help in providing glycemic control, but also prevent both macrovascular and microvascular complications. CONCLUSION Liraglutide, empagliflozin, and canagliflozin have been shown to be superior to placebo in improving CV outcomes. However, there are differences among agents in terms of HF and peripheral arterial disease outcomes. Future studies should focus on evaluating other clinical CV outcomes in patients without existing CVD and perhaps single drug regimens for diabetes.
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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.