XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been reported to predict oncologic outcomes in patients with various types of cancer. However, their prognostic value in patients with esophageal cancer is unclear. In this meta-analysis, we evaluated the prognostic significance of NLR and PLR in esophageal cancer patients. We performed comprehensive searches of electronic databases to identify studies that evaluated the prognostic impact of pretreatment NLR and PLR in esophageal cancer patients. The end points were overall survival (OS), disease-free survival, and clinicopathologic parameters. A meta-analysis using random-effects models was performed to calculate hazard ratios (HRs) or odds ratios with 95 % confidence intervals (CIs). Seven retrospective, observational, cohort studies involving 1540 patients were included. All seven studies evaluated NLR, and four evaluated PLR. Both high NLR (HR 1.40, 95 % CI 1.08–1.81, P = 0.01) and high PLR (HR 1.59, 95 % CI 1.14–2.21, P = 0.006) were significantly predictive of poorer OS. NLR was not a significant predictor of disease-free survival. High PLR (HR 1.85, 95 % CI 1.50–2.28, P < 0.00001) but not NLR was significantly predictive of poorer OS in a subgroup of patients who underwent curative surgery without neoadjuvant chemoradiation. Both high NLR and high PLR were significantly associated with deeper tumor invasion and lymph node metastasis. NLR and PLR are associated with tumor progression and are predictive of poorer survival in patients with esophageal cancer. These ratios may thus help to inform treatment decisions and predict treatment outcomes.

Prognostic Significance of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Oncologic Outcomes of Esophageal Cancer: A Systematic Review and Meta-analysis

Inflammation plays an important role in the pathophysiology of vascular disease. In this review, we consider the associations between the neutrophil-lymphocyte ratio (NLR; an indicator of inflammation) and vascular disease and its associated risk factors. The NLR has received attention due to its role as an independent prognostic factor for coronary artery disease. The NLR can also be affected by atherosclerotic risk factors, such as hypercholesterolemia, metabolic syndrome, diabetes, and hypertension. Importantly, it can predict mortality in cardiovascular diseases. There are also reports of a positive correlation between the NLR and commonly used inflammatory markers. Inflammation is important not only in pathophysiology but also clinical outcomes of many diseases. The NLR is a widely available, easily derived, and reproducible marker of inflammation. Unlike many other inflammatory markers, the NLR is inexpensive and readily available and it provides additional risk stratification beyond conventional risk scores.

https://journals.sagepub.com/doi/pdf/10.1177/1076029615569568

The Relation Between Atherosclerosis and the Neutrophil-Lymphocyte Ratio.

Arterial stiffness predicts an increased risk of cardiovascular events. Inflammation plays a major role in large arteries stiffening, related to atherosclerosis, arteriosclerosis, endothelial dysfunction, smooth muscle cell migration, vascular calcification, increased activity of metalloproteinases, extracellular matrix degradation, oxidative stress, elastolysis, and degradation of collagen. The present paper reviews main mechanisms explaining the crosstalk between inflammation and arterial stiffness and the most common inflammatory markers associated with increased arterial stiffness, considering the most recent clinical and experimental studies. Diverse studies revealed significant correlations between the severity of arterial stiffness and inflammatory markers, such as white blood cell count, neutrophil/lymphocyte ratio, adhesion molecules, fibrinogen, C-reactive protein, cytokines, microRNAs, and cyclooxygenase-2, in patients with a broad variety of diseases, such as metabolic syndrome, diabetes, coronary heart disease, peripheral arterial disease, malignant and rheumatic disorders, polycystic kidney disease, renal transplant, familial Mediterranean fever, and oral infections, and in women with preeclampsia or after menopause. There is strong evidence that inflammation plays an important and, at least, partly reversible role in the development of arterial stiffness, and inflammatory markers may be useful additional tools in the assessment of the cardiovascular risk in clinical practice. Combined assessment of arterial stiffness and inflammatory markers may improve non-invasive assessment of cardiovascular risk, enabling selection of high-risk patients for prophylactic treatment or more regular medical examination. Development of future destiffening therapies may target pro-inflammatory mechanisms.

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Inflammatory Markers for Arterial Stiffness in Cardiovascular Diseases

Endocan: A novel inflammatory indicator in cardiovascular disease?

SummaryBackground
Psoriasis vulgaris is an inflammatory disease characterized by epidermal hyperproliferation, leucocyte adhesion molecule expression and leucocyte infiltration. Psoriasis is associated with an increased risk of cardiovascular disease. Endothelial dysfunction is widely regarded as being the initial process in the development of atherosclerosis. Human endothelial cell-specific molecule-1 (endocan) is a novel human endothelial cell-specific molecule. Previous studies suggested that endocan may be a novel endothelial dysfunction marker.

Objectives
To investigate the relationship between serum levels of endocan and both cardiovascular risk and disease activity in patients with psoriasis vulgaris.

Methods
A total of 29 patients with psoriasis vulgaris and 35 control subjects were included in the study. Endocan, high-sensitivity C-reactive protein (hsCRP) and carotid artery intima–media thickness (cIMT) were measured in all subjects.

Results
Serum endocan levels were significantly different between the two groups (P < 0·001). In patients with psoriasis, serum endocan levels correlated with Psoriasis Area and Severity Index, hsCRP and cIMT (r = 0·477, P = 0·009; r = 0·484, P = 0·008; r = 0·408, P = 0·02, respectively).

Conclusions
Circulating endocan may represent a new marker that correlates with cardiovascular risk as well as the severity of disease in patients with psoriasis vulgaris. Endocan may be a surrogate endothelial dysfunction marker and may have a functional role in endothelium-dependent pathological disorders. Whether endocan levels could become a treatment target merits further investigation.

Elevated serum levels of endocan in patients with psoriasis vulgaris: correlations with cardiovascular risk and activity of disease

We read with great interest the article ‘‘Correlation of Neutrophil to Lymphocyte Ratio With the Presence and Severity of Metabolic Syndrome’’ by Buyukkaya et al. They aimed to investigate the relationship between the criteria comprising metabolic syndrome (MS) and neutrophil–lymphocyte ratio (N/L ratio) as a novel, simple, and reliable indicator of inflammation. They showed that patients with MS had significantly higher N/L ratio compared to those without MS. Furthermore, N/L ratio increased as the severity of MS increased. A strong positive correlation was revealed between the severity of MS and N/L ratio and between the severity of MS and the highsensitivity C-reactive protein (hsCRP). In addition, the correlation analysis revealed a positive correlation between hsCRP and NLR in the patient population. The measurements of white blood cells (WBCs), neutrophils, and lymphocytes in the patients with MS were higher than those without MS. The study is successful in planning and presenting the results. We believe that these findings will enlighten further studies about the association between the severity of MS and the N/L ratio. Thanks to the authors for their contribution. The WBC count is one of the useful inflammatory biomarkers in clinical practice. Leukocyte subtype and N/L ratio are also indicators of systemic inflammation. Although WBCs are in normal range, subtypes of WBCs may predict cardiovascular mortality. The N/L ratio is also an inflammatory marker of major adverse cardiac events. Some comments may be of interest. Although the authors have showed patients with MS had significantly higher N/L ratio compared to those without MS, some of the factors affecting these markers such as smoking, alcohol, and malignancy were not mentioned in this study. In addition, the authors could add a MS subgroup analysis. A subgroup analysis of MS according to age, sex, CRP, WBCs, neutrophils, and lymphocytes might affect the results of the study.

https://journals.sagepub.com/doi/pdf/10.1177/1076029612475023

Higher Neutrophil to Lymhocyte Ratio in Patients With Metabolic Syndrome

Pulse wave velocity (PWV), augmentation index (Aix), and central aortic pressure (CAP) are arterial stiffness markers of endothelial dysfunction (ED). We investigated the relationship between arterial stiffness parameters and asymmetric dimethylarginine (ADMA; a marker of ED), in newly diagnosed patients with hypertension (n = 101; 61 females). These patients were investigated in accordance with the recommendations of hypertension guidelines. Arterial stiffness was measured, and serum ADMA and C-reactive protein (CRP; a marker of inflammation) levels were determined. In both women and men, there was no difference in terms of age, body mass index, systolic and diastolic blood pressures, PWV, CAP and the levels of ADMA, while Aix and CRP levels were significantly higher in women (P = .004, P = .046, respectively). In the whole group, ADMA levels correlated with Aix (Pearson r = .237, P = .024). Our findings provide further evidence of a link between arterial stiffness and ED in newly diagnosed patients with hypertension.

Asymmetric Dimethylarginine and Augmentation Index in Newly Diagnosed Patients With Hypertension

ObjectiveThere is a growing body of data supporting the association between diabetes and microcirculatory disfunction. We aimed to study e-selectin levels, and their associations with serum markers of inflammation and arterial stiffness in prediabetes and newly diagnosed diabetes patients in this study.Subjects and methodsSixty patients (25 females) with a newly established elevated fasting serum glucose [20 impaired fasting glucose (IFG), 20 impaired glucose tolerance (IGT), 20 newly diagnosed diabetes (T2DM)] and 17 healthy controls (13 females) were included in the study. Serum e-selectin and hs-CRP levels, and arterial stiffness parameters of the patients were studied.ResultsFasting serum glucose was the most important predictor of serum e-selectin levels. Pulse wave velocity and central aortic pressures were significantly higher in IFG, IGT and T2DM groups, compared to controls (p = 0.001, < 0.001, 0.013 and 0.015, 0.002, 0.009, respectively). The mean arterial pressure did not show any significant association with serum e-selectin and hs-CRP levels (β coefficient: 0.092, p = 0.358; and β coefficient: 0.189, p = 0.362, respectively).ConclusionPrediabetes patients have increasing e-selectin levels through the diagnosis of T2DM. E-selectin is associated with serum glucose levels. Prediabetic and newly diagnosed diabetics have higher arterial stiffness measurements. Serum e-selectin may be a good marker of endothelial inflammation and dysfunction increasing in parallel with serum glucose levels, predicting future cardiovascular events.

/pdf/arterial-stiffness-and-endothelial-inflammation-in-3d5npqqr1z.pdf

Arterial stiffness and endothelial inflammation in prediabetes and newly diagnosed diabetes patients

We have read the article “Epicardial adipose tissue (EAT) is independently associated with increased left ventricular mass in untreated hypertensive (UHT) patients: an observational study” written by Erdoğan et al. (1) with a great interest. The authors aimed to evaluate the relationship between EAT and left ventricular hypertrophy (LVH) in patients with UHT. They concluded that EAT was related to increased LVM independent of body mass index (BMI), waist circumference, weight, systolic and diastolic blood pressure and other risk parameters, in patients with UHT. Determination of increased EAT by echocardiography may have an additional value as an indicator of cardiovascular risk and total visceral adipose tissue. Thanks to the authors for their contribution of the present study, which is successfully designed and documented. Cardiovascular diseases are the most important causes of mortality and morbidity in developed countries worldwide. It is widely recognized that accumulation of EAT is strongly related to the development of coronary artery disease (CAD). EAT amount may contribute to systemic inflammation beyond traditional cardiovascular risks and body fat composition. EAT measured by echocardiography has been known to be associated with metabolic syndrome (2). Additionally, echocardiography-based EAT measurement was related to several metabolic abnormalities and independently associated fatty liver disease (3). On the other hand, in kidney disease patients, EAT was positively correlated with atherosclerosis and the presence of coronary artery calcification (4). In addition, the duration of hypertension (HT) may be different in these patients. We think that the results of the study would be stronger, if the authors had mentioned these factors including the duration of HT, liver and kidney function tests. EAT can also be affected by the atherosclerotic risk factors such as alcohol consumption, hypothyroidism, impaired glucose tolerance and higher inflammatory status (5) such as an inflammatory disease, cardiac syndrome X and infection (6). In this point of view, in the present study, the authors did not mention some of these possible contributing factors. It would be better, if the authors gave information about these factors. EAT measurement with echocardiography has several advantages, including its inexpensive, easy accessibility, rapid applicability and good reproducibility. EAT has a 3-dimensional distribution and two-dimensional echocardiography cannot give adequate window of all cardiac segments especially in obese subjects and is highly dependent on acoustic windows. In this point of view, it would be better to give interobserver and intra-observer variability for EAT measurement in the current study (7). Finally, EAT itself without other inflammatory markers may not provide information to clinicians about the systemic inflammation. Therefore, we think that it should be evaluated together with other serum inflammatory markers. We believe that these findings will evaluate further studies about EAT on cardiovascular risk factors.

Muharrem Akhan

Papers

Elevated serum levels of endocan in patients with psoriasis vulgaris: correlations with cardiovascular risk and activity of disease

Higher Neutrophil to Lymhocyte Ratio in Patients With Metabolic Syndrome

Asymmetric Dimethylarginine and Augmentation Index in Newly Diagnosed Patients With Hypertension

Arterial stiffness and endothelial inflammation in prediabetes and newly diagnosed diabetes patients

Epicardial adipose tissue measurement: inexpensive, easy accessible and rapid practical method