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1.
The roles of endothelial nitric oxide synthase gene polymorphisms in diabetes mellitus and its associated vascular complications: a systematic review and meta-analysis.
Dong, J, Ping, Y, Wang, Y, Zhang, Y
Endocrine. 2018;(2):412-422
Abstract
PURPOSE The roles of endothelial nitric oxide synthase (eNOS) gene polymorphisms in diabetes mellitus (DM) were intensively analyzed, but the results of these studies were inconsistent. Therefore, we performed this study to better assess the relationship between eNOS genetic variations and DM. METHODS Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess correlations between eNOS polymorphisms and DM. RESULTS A total of 91 studies were finally included in our analyses. Significant associations with the susceptibility to DM were detected for the rs891512, rs1799983, rs2070744, and rs869109213 polymorphisms. As for vascular complications in DM, significant associations with the susceptibility to diabetic nephropathy were detected for the rs1799983 and rs2070744 polymorphisms. In addition, we also found that the rs1799983 polymorphism was significantly associated with the susceptibility to peripheral artery disease, whereas the rs2070744 polymorphism was significantly associated with the susceptibility to coronary artery disease in DM patients. Further subgroup analyses on the basis of type of disease and ethnicity of participants showed similar positive results. CONCLUSIONS In conclusion, our findings indicate that rs891512, rs1799983, rs2070744, and rs869109213 polymorphisms may serve as genetic biomarkers of DM, while rs1799983, rs2070744, and rs869109213 polymorphisms may contribute to the development of vascular complications in DM.
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Genes associated with Type 2 Diabetes and vascular complications.
Montesanto, A, Bonfigli, AR, Crocco, P, Garagnani, P, De Luca, M, Boemi, M, Marasco, E, Pirazzini, C, Giuliani, C, Franceschi, C, et al
Aging. 2018;(2):178-196
Abstract
Type 2 Diabetes (T2D) is a chronic disease associated with a number of micro- and macrovascular complications that increase the morbidity and mortality of patients. The risk of diabetic complications has a strong genetic component. To this end, we sought to evaluate the association of 40 single nucleotide polymorphisms (SNPs) in 21 candidate genes with T2D and its vascular complications in 503 T2D patients and 580 healthy controls. The genes were chosen because previously reported to be associated with T2D complications and/or with the aging process. We replicated the association of T2D risk with IGF2BP rs4402960 and detected novel associations with TERT rs2735940 and rs2736098. The addition of these SNPs to a model including traditional risk factors slightly improved risk prediction. After stratification of patients according to the presence/absence of vascular complications, we found significant associations of variants in the CAT, FTO, and UCP1 genes with diabetic retinopathy and nephropathy. Additionally, a variant in the ADIPOQ gene was found associated with macrovascular complications. Notably, these genes are involved in some way in mitochondrial biology and reactive oxygen species regulation. Hence, our findings strongly suggest a potential link between mitochondrial oxidative homeostasis and individual predisposition to diabetic vascular complications.
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Diabetes medications and cardiovascular disease: at long last progress.
Lupsa, BC, Inzucchi, SE
Current opinion in endocrinology, diabetes, and obesity. 2018;(2):87-93
Abstract
PURPOSE OF REVIEW Although intensive control of hyperglycemia has been proven to decrease the risk of microvascular complications in type 2 diabetes, it has had little apparent effect on reducing cardiovascular complications - the leading cause of mortality in this disease. We review the cardiovascular effects of various glucose-lowering medications, with a particular focus on the recent studies demonstrating clear benefits from members of several drug categories. RECENT FINDINGS Recently, several randomized controlled studies have revealed significant improvements in cardiovascular outcomes from a thiazolidinedione, two sodium-glucose cotransporter 2 inhibitors and two glucagon-like peptide 1 receptor agonists. SUMMARY These data suggest that certain glucose lowering agents after metformin should be favored in type 2 diabetes mellitus patients when there is underlying cardiovascular disease.
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Effects of glucagon-like peptide-1 receptor agonists on cardiovascular risk factors: A narrative review of head-to-head comparisons.
Dalsgaard, NB, Vilsbøll, T, Knop, FK
Diabetes, obesity & metabolism. 2018;(3):508-519
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Abstract
Cardiovascular (CV) disease is the leading cause of death and morbidity in patients with type 2 diabetes. Five CV risk factors (blood pressure, resting heart rate, body weight, cholesterol levels and blood glucose) are monitored routinely as safety and efficacy endpoints in randomized clinical trials for diabetes therapies. To determine if different glucagon-like peptide-1 receptor agonists (GLP-1RAs) had varying effects on these CV risk factors, we reviewed 16 head-to-head trials directly comparing GLP-1RAs that included at least one of the five factors. Few trials reported statistical differences between GLP-1RAs in terms of systolic blood pressure (SBP), body weight and total cholesterol. Liraglutide increased heart rate vs its comparators in three separate trials. All GLP-1RAs reduced glycated haemoglobin (HbA1c), but exenatide twice daily and lixisenatide had statistically smaller effects compared with other GLP-1RAs. These descriptive data indicate that individual GLP-1RAs affect CV risk factors differently, potentially because of their individual pharmacokinetics and/or size. Short-acting GLP-1RAs appeared to result in smaller changes in SBP and total cholesterol compared with continuous-acting treatments, while large GLP-1RAs had a reduced effect on body weight compared with small GLP-1RAs. For glycaemic control, short-acting GLP-1RAs had a greater impact on postprandial glucose levels vs continuous-acting GLP-1RAs, but for fasting plasma glucose levels and HbA1c, continuous-acting treatments had the greater effect. No differentiating trends were obvious in heart rate data. These diverse actions of GLP-1RAs on CV risk factors should aid individualized patient treatment.
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Diabetes mellitus and the risk of abdominal aortic aneurysm: A systematic review and meta-analysis of prospective studies.
Aune, D, Schlesinger, S, Norat, T, Riboli, E
Journal of diabetes and its complications. 2018;(12):1169-1174
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Abstract
BACKGROUND Diabetes mellitus has been associated with reduced risk of abdominal aortic aneurysm in a number of epidemiological studies, however, until recently little data from prospective studies have been available. We therefore conducted a systematic review and meta-analysis of prospective studies to quantify the association. MATERIAL AND METHODS Two investigators searched the PubMed and Embase databases for studies of diabetes and abdominal aortic aneurysm up to May 8th 2018. Prospective studies were included if they reported adjusted relative risk (RR) estimates and 95% confidence intervals (95% CIs) of abdominal aortic aneurysm associated with a diabetes diagnosis. Summary relative risks were estimated by use of a random effects model. RESULTS We identified 16 prospective studies with 16,572 cases among 4,563,415 participants that could be included in the meta-analysis. The summary RR for individuals with diabetes compared to individuals without diabetes was 0.58 (95% CI: 0.51-0.66, I2 = 40.4%, pheterogeneity = 0.06). The results persisted when stratified by sex, duration of follow-up, and in most of the other subgroup analyses. There was no evidence of publication bias with Egger's test, p = 0.64 or by inspection of the funnel plots. CONCLUSIONS These results suggest that individuals with diabetes mellitus are at a reduced risk of abdominal aortic aneurysm, however, whether pharmacological agents for diabetes mellitus explain this observation needs to be clarified in future studies.
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Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction.
Sorrentino, FS, Matteini, S, Bonifazzi, C, Sebastiani, A, Parmeggiani, F
Eye (London, England). 2018;(7):1157-1163
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Abstract
In the face of the global epidemic of diabetes, it is critical that we update our knowledge about the pathogenesis of diabetes and the related micro alterations on the vascular network in the body. This may ultimately lead to early diagnosis and novel treatment options for delaying the progression of diabetic complications. Research has recently revealed the pivotal role of endothelin in the pathogenesis of diabetic complications, particularly in the regulation of the capillary flow, which is affected in the course of retinopathy. Although there are several reviews on various approaches to the treatment of diabetes, including normalization of glucose and fat metabolism, no reviews in literature have focused on the endothelin system as a therapeutic target or early indicator of diabetic microangiopathy. In this review, we summarize some of the experimental and clinical evidence suggesting that current therapeutic approaches to diabetes may include the modulation of the blood concentration of compounds of the endothelin system. In addition, we will briefly discuss the beneficial effects produced by the inhibition of the production of high levels of endothelin in vasculopathy, with focus on diabetic retinopathy. The cutting-edge technology currently widely used in opththalmology, such as the OCT angiography, allows us to detect very early retinal morphological changes alongside alterations in choroidal and retinal vascular network. Combination of such changes with highly sensitive measurements of alterations in serum concentrations of endothelin may lead to more efficient early detection and treatment of diabetes and related macro/microvascular complications.
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Association of the presence of microangiopathy with adverse pregnancy outcome in type 1 diabetes: A meta-analysis.
Xiang, LJ, Wang, Y, Lu, GY, Huang, Q
Taiwanese journal of obstetrics & gynecology. 2018;(5):659-664
Abstract
OBJECTIVE Microangiopathy is common after a long duration in type 1 diabetes mellitus (T1DM). Pregnancies with end-age vascular complications are a big challenge to multidisciplinary physicians. The objective of this study was to assess the risk of microangiopathy for adverse pregnancy outcome in T1DM. MATERIALS AND METHODS PubMed, EMBASE, and Cochrane Library databases were searched for relevant articles appearing in the literature up to October 1, 2017. Analysis of cohort studies were performed with Review Manager 5.3 and Newcastle Ottawa Scale (NOS) was chosen to evaluate the risk of bias. RESULTS A total of 10 studies involving 3239 pregnancies were retrieved and analyzed. Microangiopathy for diabetic nephropathy (DN), microalbuminuria and diabetic retinopathy (DR) significantly increased the risk of preeclampsia (PE) (OR of 7.19, [95%CI: 5.15, 10.03], 4.19, [95%CI: 2.78, 6.31] and 3.02, [95%CI: 2.24, 4.07], respectively). Significant association of the presence of DN with preterm delivery was demonstrated (OR = 4.14, 95%CI [2.84, 6.02]), with small for gestation age was demonstrated (OR = 6.23, 95%CI [2.75, 14.14]) and with large for gestation age was demonstrated (OR = 0.41, 95%CI [0.27, 0.62]). A mild association of the presence of DR with preterm delivery was demonstrated (OR = 1.57, 95%CI [1.08, 2.29]). CONCLUSION The presence of microangiopathy before or in early pregnancy increased the risk of adverse pregnancy outcome in T1DM. We highlighted it was important that White's classification and a full assessment of vasculopathy should be carry out before pregnancy to ensure a well-planned pregnancy. Further work should be designed to establish risks model involving microangiopathy and find out whether early intervention with strict blood sugar control or medication such as low-dose aspirin will reduce the incidence of PE in T1DM.
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Cardiovascular benefits of combined interval training and post-exercise nutrition in type 2 diabetes.
Francois, ME, Pistawka, KJ, Halperin, FA, Little, JP
Journal of diabetes and its complications. 2018;(2):226-233
Abstract
AIM: The purpose of this study was to examine whether the combination of high-intensity interval training (HIIT) and post-exercise protein supplementation would improve cardiovascular outcomes in individuals with T2D. METHODS In a double-blind controlled trial, fifty-three adults with T2D (free of CVD and not on exogenous insulin) were randomized to 12weeks of cardio and resistance-based HIIT (4-10×1min at 90% maximal heart rate) with post-exercise milk, milk-protein, or placebo supplementation, thrice weekly. Before and after, carotid and femoral artery intima media thickness (IMT) and femoral flow profiles were assessed using high-resolution ultrasound. Central and peripheral arterial stiffness were assessed by pulse wave velocity (PWV), and resting and maximal heart rate rates were measured. RESULTS After 12weeks of HIIT femoral IMT (Pre: 0.84±0.21mm vs. Post: 0.81±0.16mm, p=0.03), carotid-femoral PWV (Pre: 10.1±3.2m/s vs. Post: 8.6±1.8m/s, p<0.01) and resting heart rate (Pre: 70.4±10.8bpm vs. Post: 67.8±8.6 bpm, p=0.01) were all significantly lower. There were no differences between nutrition groups (all significant main effects of time) for all outcomes. CONCLUSION HIIT reduces femoral IMT, arterial stiffness and resting heart rate in individuals with T2D. The addition of post-exercise milk or protein to HIIT did not have additive effects for improving cardiovascular outcomes in the present study. Taken together, HIIT alone may be an effective means to reduce the burden of cardiovascular complications in T2D.
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Stationary Treatment Compared with Individualized Chinese Medicine for Type 2 Diabetes Patients with Microvascular Complications: Study Protocol for a Randomized Controlled Trial.
Huo, J, Liu, LS, Jian, WY, Zeng, JP, Duan, JG, Lu, XJ, Yin, S
Chinese journal of integrative medicine. 2018;(10):728-733
Abstract
BACKGROUND Microvascular complications in type 2 diabetes (T2DM), including diabatic retinopathy (DR), diabetic kidney disease (DKD), diabetic peripheral neuropathy (DPN) are the leading causes of visual loss, end-stage renal disease or amputation, while the current therapies are still unsatisfactory. Chinese medicine (CM) has been widely used for treating diabetic mellitus. However, most of the previous studies focused on the single complication. The role of CM treatment in T2DM patients with 2 or multiple microvascular complications is not clear. OBJECTIVE To appraise the curative effect of CM in T2DM patients with 2 or multiple microvascular complications, and to compare the effects of stationary treatment and individualized treatment in T2DM patients with microvascular complications. METHODS This trial will be an 8-center, randomized, controlled study with 8 parallel groups. A total of 432 patients will be randomized to 8 groups: DR study group (32 cases) and a corresponding control group (32 cases), DR+DKD study group (64 cases) and a corresponding control group (64 cases), DR+DPN study group (64 cases) and a corresponding control group (64 cases), DR+DKD+DPN study group (56 cases) and a corresponding control group (56 cases). The control group will receive stationary treatment, and the study group will receive individualized treatment based on CM syndrome differentiation in addition to stationary treatment. The study duration will be 50 weeks, comprising a 2-week run-in period, 24 weeks of intervention, and 24 weeks of follow-up. The outcomes will assess efficacy of treatment, improvement in CM symptoms, safety assessments, adherence to the treatment, and adverse events. CONCLUSION This study will provide evidence of evidence-based medicine for CM treatment in two or multiple microvascular complications caused by T2DM. (Registration No. ChiCTR-IPR-15007072).
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Unilateral retinopathy in a patient with diabetes and coronary heart disease.
Abalem, MF, Eagle, KA, Rao, RC
BMJ (Clinical research ed.). 2018;:k1703