Diabetes-related Cardiovascular Complications Research Articles

Navigating the Complexity: Updates in Diabetes-Related Cardiovascular Complications

The aim of this study is to offer a thorough examination of contemporary research concerning cardiovascular complications induced by diabetes, with a specific focus on coronary artery disease (CAD), diabetic heart attacks, diabetic peripheral artery disease (PAD), and diabetic hypertension. The period of analysis spans from 1988 to 2022, and the data utilized is extracted from secondary sources. Diabetes mellitus is a chronic metabolic disorder associated with an increased risk of cardiovascular complications, including coronary artery disease (CAD), heart attacks, strokes, peripheral artery disease (PAD), and hypertension. These complications are influenced by chronic hyperglycemia, insulin resistance, dyslipidemia, inflammation, and endothelial dysfunction. Diabetic-induced cardiovascular diseases significantly contribute to morbidity and mortality rates worldwide. The studies highlight the potential of plant-derived targeted therapies in reducing inflammation and endothelial dysfunction, providing promising avenues for improving patient outcomes. Additionally, research on diabetes-specific medications, imaging techniques, individualized glycemic targets, and combination therapies reveals new approaches to managing diabetic-induced cardiovascular diseases. Precision medicine, advancements in imaging, and lifestyle interventions offer valuable tools for personalized treatment plans and improved patient care. Public health initiatives that enhance diabetes management, raise awareness, and improve healthcare access are crucial for reducing the burden of cardiovascular complications in Nigeria and other regions affected by diabetes. Further research and collaboration among healthcare professionals will refine our understanding and enhance the management of diabetic-induced cardiovascular diseases, ultimately reducing their impact on individuals with diabetes.

The role of ferroptosis in diabetic cardiovascular diseases and the intervention of active ingredients of traditional Chinese medicine.

Cardiovascular diseases (CVDs), encompassing ischaemic heart disease, cardiomyopathy, and heart failure, among others, are the most prevalent complications of diabetes and the leading cause of mortality in patients with diabetes. Cell death modalities, including apoptosis, necroptosis, and pyroptosis, have been demonstrated to be involved in the pathogenesis of CVDs. As research progresses, accumulating evidence also suggests the involvement of ferroptosis, a novel form of cell death, in the pathogenesis of CVDs. Ferroptosis, characterised by iron-dependent lipid peroxidation, which culminates in membrane rupture, may present new therapeutic targets for diabetes-related cardiovascular complications. Current treatments for CVDs, such as antihypertensive, anticoagulant, lipid-lowering, and plaque-stabilising drugs, may cause severe side effects with long-term use. Traditional Chinese medicine, with its broad range of activities and minimal side effects, is widely used in China. Numerous studies have shown that active components of Chinese medicine, such as alkaloids, polyphenols, and saponins, can prevent CVDs by regulating ferroptosis. This review summarises the recent findings on the regulatory mechanisms of active components of Chinese medicine against ferroptosis in CVDs, aiming to provide new directions and a scientific basis for targeting ferroptosis for the prevention and treatment of diabetic CVDs.

Vitamin D deficiency enhances vascular oxidative stress, inflammation, and angiotensin II levels in the microcirculation of diabetic patients

Low vitamin D (vitD) levels have been reported to be a risk factor for diabetes-related cardiovascular complications. This study examined the effects of vitD deficiency on oxidative stress (OS), inflammation, and levels of the vasoconstrictor angiotensin II (Ang II) in the microvascular tissue of type 2 diabetic patients. Patients were categorized into (i) vitD non-deficient diabetics (DNP, n = 10) and (ii) vitD-deficient diabetics (DDP, n = 10), based on their serum 25(OH)D levels. Subcutaneous fat tissues with intact blood vessels were collected during lower limb surgical procedures. The blood vessel were isolated; measurements of the antioxidant enzyme superoxide dismutase (SOD) activity, OS marker malondialdehyde (MDA), Ang II, and the inflammatory marker, TNF-α of the microvascular tissues were determined. Elevated MDA levels and reduced SOD activity, with higher levels of TNF-α and Ang II were observed in the microvascular tissues of DDP compared to DNP. VitD deficiency did not associate with glycemic parameters (fasting blood glucose and glycated hemoglobin) levels. In conclusion, vitD deficiency was correlated with higher microvascular tissue OS, inflammation, and Ang II levels in type 2 diabetic patients. This may contribute to early vasculopathy that occurs in diabetic patients, thus, may contribute to the planning of therapeutic strategies to delay or prevent cardiovascular complications.

840-P: Dual Amylin and Calcitonin Receptor Agonist Treatment Improves Blood Pressure and Glucose Control in ZSF1 Rats

Long-acting dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for the treatment of type 2 diabetes and obesity due to their beneficial effects on both body weight, glucose control and insulin action. However, whether DACRAs affect hypertension, and diabetes-related cardiovascular complications remain unknown. In this study, the cardiovascular protective effect of the DACRA KBP-336 was evaluated in obese Zucker diabetic fatty-Spontaneously hypertensive heart failure F1 hybrid (ZSF1) rats. Obese ZSF1 rats were treated for 60 days with the KBP-336 (4.5 nmol/kg Q3D) and treatment efficacy on glucose control and blood pressure measured by tail cuff was evaluated. Furthermore, serum biomarkers of cardiovascular complications were evaluated. KBP-336 treatment significantly lowered fasting blood glucose levels compared to vehicle (P<0.001). This was also illustrated in the HbA1c levels at study end, where KBP-336 resulted in significantly (P<0.001) lower levels than vehicle. Importantly, KBP-336 significantly reduced both systolic (AUC levels reduced by 13.3%, P<0.001) and diastolic (AUC levels reduced by 17.0%, P<0.001) blood pressure compared to vehicle without affecting the heart rate. Notably, the beneficial effects on both glucose control and blood pressure were obtained independent of weight loss as KBP-336 only resulted in a small and transient weight reduction. Furthermore, serum levels of the marker of cardiovascular disease, rPRO-C6 (collagen type VI formation marker) were 6.4% lower in KBP-336 treated rats compared to vehicle, supporting improvement in cardiovascular parameters. In summary, we show for the first time that KBP-336 benefits blood pressure in a metabolic rat model suffering from hypertension. In addition, KBP-336 improved glucose control independent of weight loss. These data highlight KBP-336 as a promising candidate for treating obesity and related comorbidities including type 2 diabetes and hypertension. Disclosure S.A.Melander: None. A.T.Larsen: Employee; Nordic Bioscience A/S. K.Mohamed: Employee; Nordic Bioscience. M.A.Karsdal: Speaker's Bureau; Pfizer Inc. K.Henriksen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. Funding Danish Research Foundation; Innovation Fund Denmark; European Union’s Horizon 2020 Research and Innovation Program (814244)

Recent Advances in KEAP1/NRF2-Targeting Strategies by Phytochemical Antioxidants, Nanoparticles, and Biocompatible Scaffolds for the Treatment of Diabetic Cardiovascular Complications.

Significance: Modulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated antioxidant response is a key aspect in the onset of diabetes-related cardiovascular complications. With this review, we provide an overview of the recent advances made in the development of Nrf2-targeting strategies for the treatment of diabetes, with particular attention toward the activation of Nrf2 by natural antioxidant compounds, nanoparticles, and oxidative stress-modulating biocompatible scaffolds. Recent Advances: In the past 30 years, studies addressing the use of antioxidant therapies to treat diabetes have grown exponentially, showing promising but yet inconclusive results. Animal studies and clinical trials on the Nrf2 pathway have shown promising results, suggesting that its activation can delay or reverse some of the cardiovascular impairments in diabetes. Critical Issues: Hyperglycemia- and oscillating glucose levels-induced reactive oxygen species (ROS) accumulation is progressively emerging as a central factor in the onset and progression of diabetes-related cardiovascular complications, including endothelial dysfunction, retinopathy, heart failure, stroke, critical limb ischemia, ulcers, and delayed wound healing. In this context, accumulating evidence suggests a central role for Nrf2-mediated antioxidant response, one of the most studied cellular defensive mechanisms against ROS accumulation. Future Directions: Innovative approaches such as tissue engineering and nanotechnology are converging toward targeting oxidative stress in diabetes. Antioxid. Redox Signal. 36, 707-728.

The effects of all trans retinoic acid, vitamin D3 and their combination on plasma levels of miRNA-125a-5p, miRNA-34a, and miRNA-126 in an experimental model of diabetes.

Objective:The purpose of this study was to evaluate the effects of ATRA (all trans retinoic acid), vitamin D3, and their combination on circulating levels of miR (MicroRNA) -125a-5p, miR-126, and miR-34ain diabetic rats.Materials and Methods:Total miRNA was extracted from plasma samples. miRNA expression profiles of 30 rats in five groups were analyzed after 4-week intervention. The expression levels of miRNAs were measured using qRT-PCR.Results:We analyzed the expression of miR-126, miR-125a-5p, and miR-34a in serum among all five groups (p=0.268). The levels of miRNA-126 (p=0.004) and miR-125a-5p (p=0.014) showed a significant difference among our experimental groups. The circulating levels of miR-126 decreased in DC (Diabetic control) group compared to the HC (Healthy control) group (p=0.009). In addition, vitamin D3+ATRA supplementation increased miR-126 expression (p=0.014). Moreover, the levels of miR-125a-5p decreased in the DC group compared to the HC group (p=0.019). Conclusion:The expression of miR-126 and miR-125a-5p decreased in diabetic rats. Also, vitamin D3+ATRA can be considered a new therapeutic agent that can elevate miR-126 expression and prevent diabetes-related cardiovascular complications.

IL-6 induced enhanced clearance of proANP and ANP by insulin-degrading enzyme in T1DM mice.

Cardiovascular disease (CVD) is a prevalent cause of morbidity and mortality in type I diabetes mellitus (T1DM). However, the pathophysiological mechanisms underlying the relationship between CVD, CVD risk factors, and T1DM have not yet been sufficiently explored. Here, we report that insulin-degrading enzyme (IDE) effectively degrades the precursor of atrial natriuretic peptide (proANP) in HEK293T cells. The pro-inflammatory cytokine IL-6 elicited a significant dose-dependent increase in IDE protein expression. Inhibition of the ERK/MAPK signaling pathway with selumetinib abolished the IL-6-stimulated increase in IDE protein levels and decreased ANP secretion in H9C2 cells. Importantly, the T1DM mouse model displayed lower proANP in the heart and ANP in serum, due to increased IDE expression and activity. Our results suggest a novel role of IL-6 in ANP metabolism via IDE and provide possibilities for new potential therapeutic strategies for diabetes-related cardiovascular complications.

Hyperglycaemic memory in diabetic cardiomyopathy

<p indent="0mm">Diabetes has become one of the major threats to human health worldwide. The prevalence of diabetes has accelerated significantly during the past decades with the rapid economic development in China. Cardiovascular disease accounts for 80% of the death among diabetic patients, while diabetic cardiomyopathy is one of the major diabetic cardiovascular complications. Of note, several clinical trials have demonstrated that intensive glycaemic control was able to mildly but significantly reduce the risk of myocardial infarction, but not sufficient to lower the risk of heart failure in diabetic patients. This phenomenon indicates that diabetic patients, who have been in a state of hyperglycemia, are prone to diabetes-related cardiovascular complications even after reverting to normoglycemia by hypoglycemic treatment, which is described as hyperglycemic memory (HGM). In this review, we briefly summarized the current mechanism of HGM in diabetic cardiomyopathy.

Calcitriol Supplementation Ameliorates Microvascular Endothelial Dysfunction in Vitamin D-Deficient Diabetic Rats by Upregulating the Vascular eNOS Protein Expression and Reducing Oxidative Stress.

Diabetes mellitus contributes to macro- and microvascular complications, leading to adverse cardiovascular events. This study examined the effects of vitamin D deficiency on the vascular function and tissue oxidative status in the microcirculation of diabetic rats and to determine whether these effects can be reversed with calcitriol (active vitamin D metabolite) supplementation. Streptozotocin-induced diabetic rats were fed for 10 weeks with control diet (DC) or vitamin D-deficient diet without (DD) or with oral calcitriol supplementation (0.15 μg/kg) in the last four weeks (DDS) (10 rats each group). A nondiabetic rat group that received control diet was also included (NR). After 10 weeks, rats were sacrificed; mesenteric arterial rings with and without endothelium were studied using wire myograph. Western blotting of the mesenteric arterial tissue was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) enzyme. Antioxidant enzyme superoxide dismutase (SOD) activity and oxidative stress marker malondialdehyde (MDA) levels in the mesenteric arterial tissue were also measured. The DC group had significantly lower acetylcholine-induced relaxation and augmented endothelium-dependent contraction, with reduced eNOS expression, compared to NR rats. In mesenteric arteries of DD, acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent relaxations were lower than those in DC. Calcitriol supplementation in DDS restored endothelium-dependent relaxation. Mesenteric artery endothelium-dependent contraction of DD was greater than DC; it was not affected by calcitriol supplementation. The eNOS protein expression and SOD activity were significantly lower while MDA levels were greater in DD compared to DC; these effects were not observed in DDS that received calcitriol supplementation. In conclusion, vitamin D deficiency causes eNOS downregulation and oxidative stress, thereby impairing the vascular function and posing an additional risk for microvascular complications in diabetes. Calcitriol supplementation to diabetics with vitamin D deficiency could potentially be useful in the management of or as an adjunct to diabetes-related cardiovascular complications.

Role of peroxisome proliferators-activated receptor-gamma in advanced glycation end product-mediated functional loss of voltage-gated potassium channel in rat coronary arteries

Abstract Background Voltage-gated K+ (Kv) channels in coronary artery smooth muscle cells (CSMCs), especially the major specific Kv1 subfamily, contribute to coronary artery vasodilation. Advanced glycation end products (AGEs) have been strongly implicated in diabetes-related cardiovascular complications. Our previous study showed AGEs can impair Kv channel-mediated coronary vasodilation by reducing Kv channel activity. However, its underlying mechanism remains unclear. Purpose Here, we used isolated rat small coronary arteries (RSCAs) and primary CSMCs to investigate the effect of AGEs on Kv channel-mediated coronary vasodilation and the possible involvement of peroxisome proliferators-activated receptor (PPAR)-γ pathway. Methods RSCAs and primary CSMCs were isolated, cultured and treated with bovine serum albumin (BSA), AGE-BSA, alagrebrium (ALA, AGE cross-linking breaker), pioglitazone (PIO) and/or GW9662, and then divided into the following groups: DMEM, BSA, AGE, AGE+ALA, AGE+PIO, and AGE+PIO+GW9662. Kv channel-mediated coronary vasodilation was analyzed using wire myograph. Histology and immunohistochemistry of RSCAs were performed. Western blot was used to detect the protein expression of RAGE, the major Kv1 channel subunits expressed in CSMCs (Kv1.2/1.5), PPAR-γ, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (NOX-2). Results AGEs markedly reduced forskolin-induced Kv channel-mediated vasodilation of RSCAs by interacting with the receptor for AGEs (RAGE), and ALA or PIO significantly reversed this effect. In both RSCAs and primary CSMCs, AGEs decreased Kv1.2 and Kv1.5 channel protein expression, inhibited PPAR-γ expression, increased RAGE and NOX-2 expression. Treatment with ALA or PIO partially reversed the effects of AGEs on Kv1.2/Kv1.5 expression, accompanied by elevation of PPAR-γ level and diminished oxidative stress. Conclusion AGE/RAGE axis-induced inhibition of PPAR-γ pathway and enhancement of oxidative stress may contribute to AGEs-mediated Kv channel dysfunction and coronary vasodilation in RSCAs. Our results may provide new insights into developing therapeutic strategies to manage diabetic vasculature. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China; Natural Science Foundation of Beijing (7172059)

GLP-1 receptor agonist liraglutide protects cardiomyocytes from IL-1β-induced metabolic disturbance and mitochondrial dysfunction

Cardiac inflammation plays a critical role in the development of heart failure. Inflammation-induced oxidative stress contributes to aberrant cardiac metabolism and mitochondrial function. GLP-1 receptor agonists (GLP-1 RAs) are a type of blood glucose-lowering agent typically used in the treatment of type 2 diabetes. Recent studies have convincingly shown that GLP-1 RAs possess beneficial effects in diabetes-related cardiovascular complications. Liraglutide is a commonly used long-acting agonist that shows promising cardioprotective benefits. In this study, we investigated the protective role of Liraglutide in cultured cardiomyocytes. We found that HL-1 cardiomyocytes moderately expressed the GLP-1 receptor, and co-treatment with Liraglutide ameliorated IL-1β-induced cellular ROS production and NADPH oxidase (NOX)-4 expression. Furthermore, we found that Liraglutide protected cardiomyocytes from IL-1β-induced decreased mitochondrial membrane potential and reduced ATP production. Seahorse analysis revealed that Liraglutide mitigated IL-1β-induced reduced basal and maximum respiration rates as well as spare respiration capacity. Additionally, we found that Liraglutide alleviated IL-1β-induced aberrant triglyceride accumulation and adiponectin secretion. Mechanistically, we showed that Liraglutide ameliorated IL-1β-induced phosphorylation of AMPK and ACC as well as the reduction in PGC-1α, CPT-1, and DGAT1. Finally, through the study we demonstrated that the blockage of AMPK activity by Compound C abolished the ameliorative effect of Liraglutide on IL-1β-induced repressed ATP production and triglyceride accumulation, indicating that the action of Liraglutide was dependent on AMPK activation. In conclusion, this study revealed the molecular mechanism of Liraglutide protection in cultured cardiomyocytes. The GLP-1 RA Liraglutide could have therapeutic implications by modulating cardiac inflammation.

Application of dietary supplements in the prevention of type 2 diabetes-related cardiovascular complications

Type 2 diabetes, which accounts for the vast majority of diabetes worldwide is the result of a lowered sensitivity of the insulin receptors, resulting in impaired sugar metabolism is and chronic hyperglycaemia. There is no cure for type 2 diabetes, though some people with pre-diabetes and diabetes manage to reach and hold normal blood sugar levels, thus avoiding most of the complications that come with chronic hyperglycaemia; this is sometimes referred to as ‘reversing diabetes’. A healthy diet, with sufficient amounts of fruits, nuts, and vegetables is positively correlated with maintaining glycaemic control and prevention of diabetes-related complications. Whereas many different dietary phytochemicals have been considered to play a role in the glycaemic control and in prevention of degenerative diseases, there is currently no consensus on a particular mode of action. In this review, a range of pre-clinical studies and intervention studies, including randomised double-blind, placebo controlled clinical studies, are considered that investigate the role of dietary compounds in the prevention of type 2 diabetes-related complications. Three generic mechanisms of action can be discerned: compounds that reduce sugar uptake, compounds that restore insulin function, and compounds that attenuate the effects of oxidative stress and chronic inflammation. Particularly the latter has received wide attention in the form of activation of the Nrf2-antioxidant response element signalling pathway by various polyphenolic or triterpenoid compounds. Although individual reports may present models with clear looking signalling cascades, an overall review shows that many biologically active compounds in the human diet are pan assay interference substances that alter several cell functions simultaneously, which makes them less attractive for drug development.

Targeting multiple domains of residual cardiovascular disease risk in patients with diabetes.

There has been a recent resurgence of diabetes-related cardiovascular complications after years of steady improvement. This review highlights established and emerging contemporary secondary prevention approaches that lower the risk of atherosclerotic and nonatherosclerotic cardiovascular disease events among patients with diabetes. Secondary prevention therapies modify residual risk targets, including cardiometabolic pathways, lipoproteins, thrombosis, and inflammation. Large-scale clinical trials of sodium-glucose cotransporter-2 inhibitors have demonstrated significant reductions in hospitalization for heart failure. Glucagon-like peptide-1 receptor agonists have reduced the risk of major adverse cardiovascular events. Recent clinical trials provide evidence supporting the use of nonstatin lipid-lowering therapies, novel antiplatelet and anticoagulant strategies, and antiinflammatory strategies in select cases. Therapeutic approaches targeting multiple distinct pathways have been shown to improve cardiometabolic risk in diabetes. Individual patient characteristics and consideration of residual risk targets may help guide selection of comprehensive secondary prevention approaches.

Survival and factors predicting mortality after major and minor lower-extremity amputations among patients with diabetes: a population-based study using health information systems

IntroductionThe aim of the study was to identify the sociodemographic and clinical factors associated with death after the first lower-extremity amputation (LEA), minor and major separately, using data from regional...

Ginseng for the treatment of diabetes and diabetes-related cardiovascular complications: a discussion of the evidence 1.

Diabetes mellitus (DM) is a chronic metabolic disorder associated with elevated blood glucose levels due either to insufficient insulin production (type 1 DM) or to insulin resistance (type 2 DM). The incidence of DM around the world continues to rise dramatically with more than 400 million cases reported today. Among the most serious consequences of chronic DM are cardiovascular complications that can have deleterious effects. Although numerous treatment options are available, including both pharmacological and nonpharmacological, there is substantial emerging interest in the use of traditional medicines for the treatment of this condition and its complications. Among these is ginseng, a medicinal herb that belongs to the genus Panax and has been used for thousands of years as a medicinal agent especially in Asian cultures. There is emerging evidence from both animal and clinical studies that ginseng, ginseng constituents including ginsenosides, and ginseng-containing formulations can produce beneficial effects in terms of normalization of blood glucose levels and attenuation of cardiovascular complications through a multiplicity of mechanisms. Although more research is required, ginseng may offer a useful therapy for the treatment of diabetes as well as its complications.

No Improvement in Glycemic Control or Rates of Diabetes-Related Complications for People with Type 2 Diabetes—Results from 10 Years of the International Diabetes Management Practices Study (IDMPS)

Diabetes treatment has evolved over the last decade. During this time, the IDMPS, a global observational survey on the management and patterns of care of people with type 1 and type 2 (T2D) diabetes in the developing world, has collected data in 7 individual waves. Each wave enrolled different participants. We report the glycemic condition and the frequency of diabetes-related cardiovascular complications in participants with T2D observed between 20and 2017 in 48 countries across Africa, the Middle East, South Asia, Latin America, Asia, and Eurasia. From Wave 1 to Wave 7, no improvement in the proportion of people achieving HbA1c &amp;lt;7% was seen. This is the case for all groups, i.e., those receiving oral glucose-lowering drugs (OGLDs) plus injectable treatments, and those receiving insulin (Table). The proportions of participants with micro- and macrovascular complications appear relatively unchanged. Throughout all waves, the proportion of participants receiving insulin remained constant (≈20%). For those treated with OGLDs plus basal insulin, the median daily dose of insulin was 0.21 U/kg in 20and 0.32 U/kg in 2017; over the same period, the median BMI at diagnosis increased from 26 kg/m2 to 29 kg/m2. This lack of progress highlights the continued need for improvements in diabetes management and education. Disclosure P. Aschner: Other Relationship; Self; Sanofi. J.J. Gagliardino: Other Relationship; Self; Sanofi. H.M. Ilkova: Advisory Panel; Self; Abbott, Eli Lilly and Company, Novartis AG, Novo Nordisk A/S, Boehringer Ingelheim GmbH, Servier, Merck Sharp &amp; Dohme Corp.. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Medtronic, Roche Diabetes Care Health and Digital Solutions, Bilim İlac. F.J. Lavalle-Gonzalez: Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Research Support; Self; AstraZeneca. Advisory Panel; Self; Merck Sharp &amp; Dohme Corp.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Abbott. A. Ramachandran: None. G. Kaddaha: Other Relationship; Self; Sanofi. J. Mbanya: Advisory Panel; Self; GlaxoSmithKline plc.. Speaker's Bureau; Self; Novo Nordisk A/S, Sanofi, Servier. M.V. Shestakova: None. J. Chantelot: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. J.C. Chan: Consultant; Self; Bayer AG. Other Relationship; Self; Bayer AG. Consultant; Self; Sanofi. Other Relationship; Self; Sanofi, Eli Lilly and Company, Amgen Inc.. Consultant; Self; AstraZeneca, Merck &amp; Co., Inc., Pfizer Inc.. Other Relationship; Self; Pfizer Inc.. Board Member; Self; Asia Diabetes Foundation. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; Merck Sharp &amp; Dohme Corp.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novartis AG, Eli Lilly and Company.

The association between various smoking behaviors, cotinine biomarkers and skin autofluorescence, a marker for advanced glycation end product accumulation.

BackgroundSkin autofluorescence, a biomarker for advanced glycation end products (AGEs) accumulation, has been shown to predict diabetes-related cardiovascular complications and is associated with several environmental and lifestyle factors. In the present study, we examined the association between various smoking behaviors and skin autofluorescence, as well as the association between several cotinine biomarkers and skin autofluorescence, using both epidemiological and metabolomics data.MethodsIn a cross-sectional study, we evaluated participants from the LifeLines Cohort Study and the Qatar Metabolomics Study on Diabetes (QMDiab). In the LifeLines Cohort Study smoking behavior and secondhand smoking were assessed in 8,905 individuals including 309 individuals (3.5%) with type 2 diabetes. In QMDiab, cotinine biomarkers were measured in saliva, plasma and urine in 364 individuals of whom 188 (51%) had type 2 diabetes. Skin autofluorescence was measured non-invasively in all participants using the AGE Reader.ResultsSkin autofluorescence levels increased with a higher number of hours being exposed to secondhand smoking. Skin autofluorescence levels of former smokers approached levels of never smokers after around 15 years of smoking cessation. Urinary cotinine N-oxide, a biomarker of nicotine exposure, was found to be positively associated with skin autofluorescence in the QMDiab study (p = 0.03).ConclusionsIn the present study, we have demonstrated that secondhand smoking is associated with higher skin autofluorescence levels whereas smoking cessation has a beneficial effect on skin autofluorescence. Finally, urinary cotinine N-oxide might be used as an alternative way for questionnaires to examine the effect of (environmental) tobacco smoking on skin autofluorescence.

Polydatin Restores Endothelium-Dependent Relaxation in Rat Aorta Rings Impaired by High Glucose: A Novel Insight into the PPARβ-NO Signaling Pathway.

Polydatin, a natural component from Polygonum Cuspidatum, has important therapeutic effects on metabolic syndrome. A novel therapeutic strategy using polydatin to improve vascular function has recently been proposed to treat diabetes-related cardiovascular complications. However, the biological role and molecular basis of polydatin’s action on vascular endothelial cells (VECs)-mediated vasodilatation under diabetes-related hyperglycemia condition remain elusive. The present study aimed to assess the contribution of polydatin in restoring endothelium-dependent relaxation and to determine the details of its underlying mechanism. By measuring endothelium-dependent relaxation, we found that acetylcholine-induced vasodilation was impaired by elevated glucose (55 mmol/L); however, polydatin (1, 3, 10 μmol/L) could restore the relaxation in a dose-dependent manner. Polydatin could also improve the histological damage to endothelial cells in the thoracic aorta. Polydatin’s effects were mediated via promoting the expression of endothelial NO synthase (eNOS), enhancing eNOS activity and decreasing the inducible NOS (iNOS) level, finally resulting in a beneficial increase in NO release, which probably, at least in part, through activation of the PPARβ signaling pathway. The results provided a novel insight into polydatin action, via PPARβ-NO signaling pathways, in restoring endothelial function in high glucose conditions. The results also indicated the potential utility of polydatin to treat diabetes related cardiovascular diseases.

Use of the Drug Burden Index to identify and reduce potentially inappropriate prescribing of anticholinergic and sedative agents in elderly patients in institutionalized care: a systematic review protocol

Review question/objective The aim of this review is to critically appraise, synthesize and present evidence on the use of the Drug Burden Index (DBI) to identify and reduce potentially inappropriate prescribing of anticholinergic and sedative agents in elderly patients in institutionalized care. More specifically, this review seeks to answer the following questions: 1.In which specific settings and patient groups has the Drug Burden Index been applied? 2.Which outcomes have been studied? (E.g. occurrence and incidence of adverse drug reactions, physical functioning, mental functioning, cause of admission to hospital, etc.) 3.Has the use of the Drug Burden Index impacted upon inappropriate prescribing of anticholinergic and sedative agents to elderly patients in institutionalized care? (E.g. cessation of therapy, prescribing altered to other agents, reduction in adverse drug reactions, etc.) Inclusion criteria Types of participants The focus of this review will specifically be on ‘elderly patients’ as described within the studies. If no classification is given within studies, then only those studies reporting on patients aged 65 years and over will be included in the review. Furthermore, patients receiving care within either hospital or care home settings (institutionalized care) will be included in the review. The care of these patients and hence the use of the Drug Burden Index is likely to be markedly different to home dwelling patients. Types of intervention(s) Use of the Drug Burden Index tool to identify and reduce potentially inappropriate prescribing of anticholinergic or sedative medications. Types of comparisons Patients with a score of zero on the Drug Burden Index (i.e. no prescription of anticholinergic or sedative medicines) compared to the Drug Burden Index score; or different levels of Drug Burden Index scores between sub-samples of patients. Most studies will have no comparison. Types of outcomes This review will consider studies that include the following outcome measures: 1.Drug Burden Index scores 2.Physical and mental functioning; adverse effects of anticholinergic and sedative medicines 3.Changes to therapy following application of the Drug Burden Index as a tool to identify potentially inappropriate prescribing

Increasing age associated with elevated cardio–ankle vascular index scores in patients with type 2 diabetes mellitus

The study investigated the relationship between arterial stiffness calculated using the cardio-ankle vascular index (CAVI), diagnosis of type 2 diabetes mellitus and type 2 diabetes-related cardiovascular complications, in patients with type 2 diabetes mellitus (type 2 diabetes) and nondiabetic patients. A retrospective cross-sectional study was conducted in patients with type 2 diabetes and age-matched nondiabetic patients. CAVI was measured using an automatic vascular screening system. Parameters associated with type 2 diabetes and cardiovascular complications were also measured. A total of 51 patients with type 2 diabetes and 59 nondiabetic patients were enrolled in the study. Significantly higher CAVI scores were observed in patients with type 2 diabetes compared with nondiabetic patients (mean ± SD: 9.55 ± 1.13 versus 8.54 ± 0.94, respectively). Multivariate linear regression analyses demonstrated that age was the only significant factor influencing the CAVI score, in patients with type 2 diabetes. Patients with type 2 diabetes had an increased risk of arterial stiffness, based on the CAVI score, compared with nondiabetic patients; this, in turn, could increase their risk of developing other cardiovascular complications.