Clinical guidelines for type 2 diabetes mellitus honda,meteovista lier,type 2 diabetes diet bbc mosley - 2016 Feature


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Discuss various statistics regarding diabetes mellitus, including its prevalence in the United States. Differentiate between type 1 and type 2 diabetes, including pathogenesis and prevalence for each type. List and explain the various tests and methodologies used for the identification of diabetes.
Discuss various features of hemoglobin A1c and other glycated proteins, including fructosamine and glycoalbumin and their use in the detection of diabetes.
Explain long-term monitoring of diabetes mellitus, including the use of estimated average glucose. Although simply defined on the basis of hyperglycemia, diabetes mellitus today is known to be a highly heterogeneous disease. In the past, the diagnosis of diabetes was based on either fasting plasma glucose or two-hour plasma glucose level in the oral glucose [75 g] tolerance test (OGTT). The glycation of hemoglobin occurs at several amino acid residues and, as a result, several adducts of hemoglobin A (HbA) and various sugars are formed by the nonenzymatic post-translational glycation process. Various methods for the measurement of HbA1c have been described and reviewed.6 These methods can be classified in two major categories.
Because of their ability to process a large number of samples and their superior precision, automated HPLC and automated immunoassays are among the most widely used methods. Besides the standardization of various methods, one may also be aware of the clinical situations in which HbA1c may not provide an accurate estimation of glycemic control. Several assays designed to measure glycated serum proteins (fructosamine and GA) have been described. Despite these limitations, measuring fructosamine or GA provides some advantages over measuring glycohemoglobin A1c as they are not affected by RBC life span, and the glycated protein levels respond more quickly to changes in glycemic control than glycohemoglobin A1c.
The effective clinical management of diabetes requires accurate measurement and monitoring of blood glucose levels.
Several studies have explored the relationship between HbA1c and chronic glycemia and have supported the association of HbA1c with average glucose levels over the preceding five to 12 weeks.17 These studies have relied on infrequent measures of capillary glucose levels, calling into question the validity of their assessment of chronic glycemia. Recently, HbA1c has been incorporated into diabetes diagnosis, and is recommended by the International Expert Committee based on advances in instrumentation and standardization that make it an accurate and precise marker.
International expert committee report on the role of the A1c assay in the diagnosis of diabetes. All treatment options shown may be appropriate, and final selection of therapy should be individualized based on patient eligibility and treatment availability at the physician's discretion.
All treatment options shown may be appropriate and final selection of therapy should be individualized based on patient eligibility and treatment availability at the physician's discretion. Consensus statement policyThe Institute of Medicine's March 2011 Standards for Developing Trustworthy Clinical Practice Guidelines13 served as a model for organising and preparing this consensus statement. Consensus management of stage II melanomaThe panel is divided on the role of immunotherapy for patients with high-risk stage II melanoma (Figure 1) and recognizes the limited level A data available to inform clinical decision-making. With a few notable exceptions, the American Diabetes Association (ADA) recommendations for treatment of elevated LDL-C generally follow the recommendations of the 1993 ADA Consensus Development Conference and the NCEP ATP III guidelines.
Medical nutrition therapy and a physical activity plan should be attempted before initiating drug therapy. This slide was created under the auspices of Professional Postgraduate Services® through an unrestricted educational grant. Search the NHLBI, use the drop down list to select: the entire site, the Health Topics section only, or the News and Resources section.
This section presents the results of a critical review of the evidence that atherosclerosis begins in childhood and that this process, from its earliest phases, is related to the presence and intensity of known cardiovascular (CV) disease (CVD) risk factors (see Table 2?1). Figure 2-1 depicts the pathologic progression of atherosclerosis with aging, from no visible atherosclerosis at birth to the development of complex plaques with potential rupture and thrombosis in mid- to late adulthood.
The most important evidence for the relationship of childhood risk factors to CVD is the establishment of a direct relationship between risk exposure and events. Thus, studies examining the clinical importance of CV risk in childhood must consider end points recognized as intermediate stages in the pathogenesis of CVD. Legend to Figure 2?2: This flow diagram depicts the timeline for development of cardiovascular (CV) risk, atherosclerosis, and CV events along a continuum extending from before birth to adult life.
Considered collectively, these studies constitute an evidence chain, with the strength of the body of evidence represented in the evidence grades. Atherosclerosis at a young age was first identified in Korean War and Vietnam War casualties.[5],[6] Two major contemporary studies, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) and the Bogalusa Heart Study (Bogalusa), have subsequently demonstrated atherosclerosis, indicated by fatty streaks and more advanced lesions, in children, adolescents, and young adults who died as a result of unintentional injury.
Figure 2?3, from the PDAY study, shows the relationship between the number of identified CV risk factors and the pathologic lesions of atherosclerosis by age in the right coronary artery, using maps of arterial segments created by converting pathologically classified lesions to computerized images. These computerized images from the Pathobiological Determinants of Atherosclerosis in Youth study are prevalence maps of fatty streaks and raised lesions, with color intensity reflecting the density and grade of the lesions for the two age groups and the number of risk factors. Measures of subclinical atherosclerosis and end organ injury include the presence of coronary calcium on electron beam computerized tomography (EBCT) imaging, increased medial thickness of the carotid artery assessed with ultrasound (cIMT), reduced endothelium-dependent dilation of the brachial artery with ultrasound imaging (flow-mediated dilation (FMD)), and increased left ventricular mass (LVM) by cardiac ultrasound. Subclinical atherosclerosis imaging studies (coronary calcium by EBCT, cIMT) have been important in demonstrating the importance of childhood risk factors to future atherosclerosis.
The most important evidence relating risk in childhood to clinical CVD is the observed association of risk factors for atherosclerosis to clinically manifest CV conditions. As described above, there is evidence to indicate that hypertension, dyslipidemia, diabetes, obesity, and cigarette smoking—established risk factors for CVD in adults—contribute to the early development of atherosclerosis, with the exception of two risk factors.
CVD has been observed in diverse geographic areas and in all racial and ethnic backgrounds. Although genetic dyslipidemias and diabetes mellitus are recognized as high-risk states, from a population standpoint, it is the clustering of multiple risk factors that is most commonly associated with premature atherosclerosis.
The relationship of the current obesity epidemic in children to future CVD and diabetes in adulthood is considered one of the most important public health challenges in the United States, particularly given the fact that more than 30 percent of the U.S.
Tracking studies from childhood to adulthood exist for all the major risk factors, including obesity, dyslipidemia, diabetes, cigarette smoking, and hypertension. It is important to distinguish between the goals of prevention at young ages and such goals at older ages when atherosclerosis is well-established, morbidity already may exist, and the process is only minimally reversible (Figure 2?2). The most direct means of establishing evidence for active CVD prevention beginning at a young age would be to randomize young individuals with defined risks to treatment of CV risk factors or to no treatment and then to follow both groups over sufficient time to determine whether CV events are prevented without undue increase in morbidity arising from treatment.
The recognition that evidence from this direct pathway is unlikely to be obtained requires an alternate stepwise approach, linking segments of an evidence chain in a manner that serves as a sufficiently rigorous proxy for the causal inference of a clinical trial. The remaining evidence links pertain to the determination of whether interventions that aim to reduce risk factors will have a health benefit and whether the risk and cost of interventions to reduce risk are outweighed by the reduction in CVD morbidity and mortality.
Intervention planning must consider that each risk factor exists within an individual's unique combination of environmental, behavioral, physiologic, and genetic characteristics. For certain behavioral risk factors, limitations in measurement and data collection make the establishment of a causal pathway between the risk factor and disease impossible. Since risk levels in the preadolescent pediatric population with normal weight for height are generally below levels associated with CV events,[113] a critical component of pediatric CVD prevention is understanding those factors associated with the evolution from the low-risk state of childhood to the presence of risk in adulthood. A new consideration is the role of new noninvasive measures of cardiac and vascular injury in the evaluation of evidence. Thus, for each risk factor discussed in the sections below, recommendations reflect a complex decision process that integrates the strength of the evidence with knowledge of the natural history of atherosclerotic vascular disease, estimates of intervention efficacy and risk, and the physician's responsibility to provide both health education and effective disease prevention and treatment. Recently, the International Expert Committee (2009) and the ADA Clinical Practice Guidelines (just published in 2013) recommended the use of glycated hemoglobin (HbA1c) to diagnose diabetes.2-3 This article will review the current state of the laboratory testing with special focus on the role of  HbA1c and other emerging glycated protein biomarkers, including fructosamine and glycated albumin (GA), in the diagnosis and long-term monitoring of diabetes. For decades the diagnosis of diabetes mellitus (type 1 and type 2) was made on the basis of an elevated fasting glucose level. Furthermore, in spite of standardization, many factors, including noncompliance for fasting and inability to tolerate the glucose load, among many other factors, influence the final test outcome. Glycemic biomarkers are important tools to monitor glycemic control.5 Measurement of glycated proteins, primarily HbA1c, has been widely used for routine long-term monitoring of glucose control and as a measure of risk for the development of diabetes complications. Hemoglobin A1c was first discovered in 1969 as an abnormal hemoglobin fraction in blood from diabetes patients.
This process involves the formation of a labile Schiff base intermediate followed by the Amadori rearrangement.
One category is based on separation and detection of HbA1c on the basis of charge differences and includes ion-exchange chromatography, high performance liquid chromatography (HPLC), and agar gel electrophoresis.
Glycation of HbA1c not only depends on average glycemia but also on the rate of production or destruction of RBCs. Like glycohemoglobin, glucose molecules are joined to protein molecules through a nonenzymatic glycation mechanism to form stable ketoamines termed fructosamine. However, these assays are currently used only to complement glycohemoglobin A1c assays to manage diabetic patients when the detection of short-term metabolic changes is required. Traditionally, plasma glucose has been the lab test used for monitoring the patient with diabetes.
More recently, an international multicenter study examined the relationship between average glucose, as assessed with a combination of continuous glucose monitoring and frequent finger-stick capillary glucose testing and HbA1c levels over time, and demonstrated a close relationship between the two. Currently HbA1c is widely used as a glycemic marker for long-term monitoring of diabetes, as it provides valuable information about the degree of glucose control during the previous eight to 12 weeks. Repeatability of the oral glucose tolerance test for the diagnosis of impaired glucose tolerance and diabetes mellitus. Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Defining the relationship between plasma glucose and HbA1c in the Diabetes Control and Complications Trial. The goal of this article is to provide evidence-based consensus recommendations for the use of immunotherapy in the clinical management of patients with high-risk and advanced-stage melanoma in the USA.
These standards include establishing a transparent process for guideline development and funding, managing and reporting conflicts of interest, inclusion of a multidisciplinary and balanced group composition, establishing an evidence-based foundation and rating system for the strength of the evidence, reporting the results through a peer-reviewed publication and publicly available website, and having a plan for updating the statement as changes in the field warrant revisions. This workup should include sentinel-lymph-node biopsy, when appropriate.3, 16 There is general agreement that patients with low-risk stage II melanoma can be safely observed and do not warrant treatment (Figure 1).
The majority of the panel recommends that high-risk patients be treated with standard 1-year interferon-α2b, although a minority suggest participation in clinical trials (assuming availability and eligibility to the protocol-specific patient selection criteria of the trial) or observation. Each risk factor exists within a behavioral, environmental, physiologic, and genetic context that provides the rationale for its consideration as a risk factor that could be used to identify persons who are at elevated risk or who may be the target of intervention.
This evidence is best obtained from long-term observational studies beginning in childhood, with risk factors measured and related to CVD outcomes later in life. The chart flows in one direction with arrows pointing downward and lateral arrows to one or more boxes. Studies evaluated for the Guidelines may have examined single links in the chain of evidence, may have connected several links simultaneously, or may have evaluated the consequences of specific interventions for risk-benefit analysis. In the Bogalusa study, CV risk factors (lipids, blood pressure, body mass index (BMI), tobacco use) were measured as part of a comprehensive school-based epidemiologic study of a biracial community. These are displayed as prevalence maps of fatty streaks and raised lesions, with color intensity reflecting the density and grade of the lesions.[13] In 15- to 24-year-old subjects, the maps demonstrate the impact of increasing numbers of risk factors on both the presence and severity of the atherosclerotic process.
Genetic disorders related to high cholesterol are the biologic model for risk factor impact on the atherosclerotic process. As demonstrated in the PDAY, CARDIA, Young Finns, and Bogalusa studies and as shown in Figure 2?3, the presence of multiple risk factors is associated with striking evidence of an accelerated atherosclerotic process. At middle age and older, the goals are to prevent clinical events from occurring and to minimize the risk of future events in those with existing morbidity.


This direct approach is attractive because atherosclerosis prevention would begin at the earliest stage of the disease process, thereby maximizing benefit. Figure 2?2 demonstrates the components of this evidence chain, with links comprising a series of critical studies leading from risk beginning before birth, to risk acquisition during childhood, to risk modification by reduction strategies, and finally to clinical disease in adulthood. There is unlikely to be a study comparing the effect of a lifetime of whole-milk consumption with fat-free milk consumption, or a study comparing daily physical training for decades with a lifetime of inactive television watching on the amount of atherosclerosis or rates of myocardial infarction. The well-established factors on this environmental-behavioral axis are initiating tobacco use and becoming obese. These recommendations for providers of health care to children will be most effective when complemented by a broader public health strategy, as discussed in Section XVI. One cornerstone of pediatric care is placing clinical recommendations in a developmental context. Based on the results of the evidence review, the Guidelines provide recommendations for preventing the development of risk factors and optimizing CV health beginning in infancy. Comparison of coronary heart disease risk factors in autopsied young adults from the PDAY Study with living young adults from the CARDIA study. Risk factors related to carotid intima-media thickness and plaque in children with familial hypercholesterolemia and control subjects. Usefulness of electron beam tomography in adolescents and young adults with heterozygous familial hypercholesterolemia.
Carotid artery intimal-medial thickness and left ventricular hypertrophy in children with elevated blood pressure. Intima media thickness in childhood obesity: relations to inflammatory markers, glucose metabolism, and blood pressure.
Left ventricular geometry and severe left ventricular hypertrophy in children and adolescents with essential hypertension. Vascular function and carotid intimal-medial thickness in children with insulin-dependent diabetes mellitus.
Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes.
Early atherosclerosis in childhood type 1 diabetes: role of raised systolic blood pressure in the absende dyslipidaemia. Increased carotid intima-media thickness in children, adolescents and young adults with a parental history of premature myocardial infarction.
Parental occurrence of premature cardiovascular disease predicts increased coronary artery and abdominal aortic calcification in the Framingham Offspring and Third Generation cohorts.
Endothelium-dependent dilatation is impaired in young healthy subjects with a family history of premature coronary disease.
Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Type 1 diabetes is characterized by absolute insulin deficiency due to autoimmunity leading to ?-cell destruction and can be identified by serological markers of autoimmunity (islet cell autoantibodies). The ADA proposes that fasting plasma glucose (FPG) should be measured in all asymptomatic people ?45 years of age and screening should be considered at a younger age in individuals at increased risk for diabetes.
Based on current recommendations from the National Diabetes Data Group, the OGTT must be done after three days on a diet containing a minimum of 150 g of carbohydrates per day. The test accurately assesses the mean blood glucose level during the preceding two to three months; therefore, it complements the more traditional measures of glucose control (blood or urine glucose testing).
It was later shown that glucose binds to hemoglobin in red blood cells, and the term “glycohemoglobin” is applied to a number of chemically distinct hemoglobin components that are generated when glucose binds to hemoglobin. The reaction is slow, continuous, and irreversible, and the reaction rate depends on the ambient glucose concentration. There is no convincing data to show that one method is superior to the other, as practically all commercial methods are standardized to a common reference standard. Findings from the Diabetes Control and Complication Trial demonstrate that maintaining blood glucose close to normal reduces diabetes complications.17 This study compared the standard versus intensive blood glucose control on the complications of diabetes.
It is also being used as a primary treatment target, as it has been shown to have close association with diabetes complications. However, it should be reiterated that there are some limitations, and HbA1c may not provide accurate information in certain clinical situations that affect RBC life span—for example, certain hemoglobulinopathies (hemoglobin S, C, or E), anemia, and renal dysfunction.
Melanoma can be highly sensitive to immunotherapy and of the six approved drugs highlighted above only dacarbazine and vemurafenib are not immunotherapies. Convening under the umbrella of SITC (June 2011), a steering committee led a panel, which sought to develop clinical treatment guidelines considering four basic issues for each immunotherapy agent in current clinical practice: patient selection, toxicity management, assessment of response, and therapy sequencing and combinations. A few panellists (5%) individualize treatment of patients with high-risk stage II melanoma based on the particular situation.
Introduction, the literature search for these Guidelines addressed 14 critical questions (I. The progression of atherosclerosis is exacerbated and intensified by the presence of risk factors. Because of the time course of atherosclerosis, studies of 50 to 60 years' duration linking early risk to CV events are impractical, although studies exist in which risk was measured in early adulthood and outcomes were measured much later in life.
Studies describing environmental or behavioral factors that affect the process are shown on the left side, and potential pathophysiologic or medical actions are shown on the right.
Below, the flow chart is described as lists in which the possible next steps are listed beneath each box label. Although each study is graded individually in the evidence tables, the Expert Panel assigned summary grades for the body of evidence reviewed in developing each recommendation.
Prevention of atherosclerosis development receives greater emphasis in children and young adults. Findings were related to atherosclerosis measured at autopsy after accidental death, and strong correlations were shown between the presence and intensity of risk factors and the extent and severity of atherosclerosis.[3],[7] In the PDAY study, risk factors and surrogate measures of risk factors were measured post mortem in 15- to 34-year-olds who died accidentally of external causes.
Comparison with 25- to 34-year-olds shows the impact of both age and multiple risk factors. Alex McMahan for the Pathobiological Determinants of Atherosclerosis in Youth Study Group, unpublished observation. Studies directly relating fitness levels in childhood to future atherosclerosis have not been performed. Several longitudinal cohort studies referenced extensively in these Guidelines (Bogalusa, PDAY, Coronary Artery Risk Development in Young Adults (CARDIA)) examine biracial populations, although longitudinal data for Hispanic, Native American, and Asian children are lacking. The two most prevalent multiple risk combinations are tobacco use with one other risk factor[74] or the development of obesity, which often is associated with insulin resistance (as opposed to elevated blood sugar in adults), elevated triglycerides, reduced HDL?C, and elevated blood pressure. Among the many studies demonstrating this tracking,[72],[92],[93],[94] one of the most recent is a report from the Bogalusa study, which followed more than 2,000 children from 5 to 14 years of age at initial evaluation to adult followup at a mean age of 27 years. At a young age, historically there have been two goals of prevention: (1) prevent the development of risk factors (primordial prevention) and (2) recognize and manage those children and adolescents at high risk due to the presence of one severe risk factor or multiple risk factors (primary prevention). That does not diminish the critical importance of public health measures to CVD prevention.
Studies evaluated for these Guidelines may examine single links in this evidence train, connect several links simultaneously, or evaluate the consequences of specific interventions to allow risk-benefit analysis. Introduction, Table 1?1, questions 9?14), which are addressed subsequently in the evidence review of each risk factor.
A family history showing multiple members affected by clinical CVD at a young age suggests the need to investigate both genetic risk and toxic environmental exposure and to consider early risk reduction. What is important about diet and exercise in childhood is the relationship of healthful behaviors to the development of future risk factors, including obesity, diabetes mellitus, hypertension, and dyslipidemia.
Although the evidence for a heart healthy diet and physical activity in the treatment of established risk factors is strong, less strong but emerging evidence suggests that an energy-balanced, nutrient-dense diet and consistent routine levels of physical activity that promote physical fitness prevent risk factor acquisition over the course of decades.
For adults, the primary use of these technologies has been in event prediction; that is, whether the presence of one of these markers increases the likelihood of a future CV event beyond that expected from conventional risk factor assessment. As opposed to virtually universal recommendations that apply to nearly all adults, pediatric recommendations must consider not only the relationship of age to disease expression but also the ability of the child and the family to understand and implement medical advice and the safety of the intervention modality.
Pediatric care providers—pediatricians, family practitioners, nurses and nurse practitioners, physician assistants, and registered dietitians—are ideally positioned to reinforce these CV health behaviors as part of routine care. The three-to-five hour oral glucose tolerance test, once the gold standard for diagnosing diabetes, is currently not recommended either by the ADA or the International Expert Committee.2-3 However, both the ADA and International Expert Committee continue to recommend use of the two-hour oral glucose challenge test, especially in gestational diabetes mellitus (GDM). The clinical utility of insulin measurement is limited, primarily because when fasting glucose is elevated, ?-cell responsiveness decreases, and when the fasting glucose level is normal, late hyperinsulinism may occur in type 2 diabetes or in the early phase of type 1 diabetes.
In addition to hemoglobin, other proteins in blood can also be glycated, and glycated proteins such as fructosamine and glycoalbumin (GA) can also be measured and used as an estimation of glucose control.5 Today the use of HbA1c is also recommended by the ADA and other organizations for diabetes screening and diagnosis. Minor components of HbA were first recognized because of the differences in their electrical charges and were called “fast hemoglobin” as they migrated at a faster rate than an entire HbA molecule when placed in an electrical field. Albumin is the most abundant serum protein, and it contains multiple lysine residues, all of which can be glycated.
There are clinical situations in which fructosamine or GA should not be used, such as for thyroid disease (as in thyrotoxic or hypothyroid patients in whom protein turnover is increased or decreased). Now HbA1c levels can be expressed and reported as eAG for most patients with type 1 or type 2 diabetes. Furthermore, its value can be translated into eAG values, providing valuable information to clinicians in monitoring patients with diabetes.
If a discrepancy between blood glucose and HbA1c is observed, one must consider the measurement of extracellular glycated proteins (fructosamine or GA), as these are not affected by RBC life span or iron status. The Institute of Medicine clinical practice guidelines were used as a basis for this consensus development.
There was level B data for a clinical benefit with surgical resection of completely resectable lesions and first-line surgical resection was a minority opinion (9%) of the consensus panel. This consensus statement is not intended to substitute for the individual professional judgement of the treating physician. None of the panel members recommends treatment with pegylated-interferon-α2b for patients with high-risk stage II disease. Clinical trials of voluntary risk exposure, in which children would be randomized at birth to become, for example, chronic smokers, to determine the likelihood of future heart attack decades later, would be both impractical and unethical. Also relevant are studies of factors associated with the development of risk factors, such as a high-fat diet and a physically inactive lifestyle. The complexity of the evidence development process is apparent in the multiple interrelationships between risk factors that change and evolve throughout the history of each individual from childhood to adulthood. The many evidence pathways pursued in preventive cardiology research and included in the evidence reviewed for the Guidelines are displayed in Figure 2?2. In older adults, importance is placed on factors associated with the progression of atherosclerosis and factors associated with acute events, such as predisposition to thrombosis or plaque instability. Strong relationships were demonstrated between atherosclerotic severity and extent and the presence and intensity of known risk factors, including higher age, higher non-high-density lipoprotein cholesterol (non-HDL?C), lower HDL cholesterol (HDL?C), hypertension (determined by renal artery thickness), tobacco use (thiocyanate concentration), diabetes mellitus (glycohemoglobin), and obesity in males. Risk, particularly the presence of multiple risk factors, accelerates the development of atherosclerosis. Clinically important differences in the prevalence of risk factors exist by race and gender, particularly with regard to tobacco use rates, obesity prevalence, hypertension, and dyslipidemia.
This latter combination, known as the metabolic syndrome in adults, has become increasingly prevalent in childhood. Based on BMI percentiles derived from the study population, 84 percent of those with a BMI in the 95th to 99th percentiles as children were obese as adults.[95] For obesity, increased correlation is seen with increasing age at which the elevated BMI is obtained. With the development of measures of subclinical atherosclerosis, left ventricular hypertrophy, and endothelial function, the potential to assess a third goal has emerged: documentation of the prevention of the early stages of atherosclerosis and other forms of CV pathology.


For risk factors such as tobacco use and physical inactivity, public health measures are critical for risk reduction.
Such a study would be extremely expensive and would require a high level of adherence and participant retention over several decades, during which time changes in environment and medical practice would diminish the relevance of the results. Some studies encompass the entire lifespan, whereas others examine the impact of interventions on intermediate states.
The best evidence for answering these questions derives from randomized trials showing event reduction in adults, randomized trials in children showing risk reduction with change in subclinical measures of atherosclerosis or target organ damage and patient safety, genetic studies that provide a model for the adverse effects of sustained exposure to risk, and long-term observational studies demonstrating the benefit of maintenance of low risk on health and all-cause mortality. Consequently, recommendations must include studies that examine the impact of interventions on risk factor development and reduction rather than studies that only examine the effects on subclinical disease measures or clinical events.
The Guidelines also offer specific guidance on primary prevention, with age-specific, evidence-based recommendations for individual risk factor detection. Patients and families expect physicians, nurses, dietitians, and other health care providers and counselors to provide accurate health information.
Today, diabetes-associated complications remain the leading cause of heart disease- or stroke-related deaths and are associated with long-term damage including the failure of organs such as eyes and kidneys.
Type 2 diabetes is caused by insulin resistance and lack of compensatory insulin secretory response. However, it has some limitations, indicating the need for the use of other glycated protein biomarkers. Also, HbA1c levels can be false high in situations that increase the production of RBCs, as in patients with chronic kidney disease who receive erythropoietin for anemia or in patients who receive a blood transfusion.11 In brief, HbA1c levels are shown to be positively associated with hemoglobin levels and are negatively associated with erythropoietin dose.
Levels are also influenced by low albumin levels, as seen in patients with protein-losing enteropathy, nephritic syndrome, or liver failure.
Today, use of HbA1c is accepted as a long-term monitoring tool for the management of diabetic patients and is used in conjunction with plasma or finger-stick glucose testing. The calculated eAG level gives healthcare providers a more useful index of chronic glycemia. However, their relationship to average glucose and their prognostic value to diabetes complications are not clear, as in the case of HbA1c.
A systematic literature search was performed for high-impact studies in English between 1992 and 2012 and was supplemented as appropriate by the panel.
Although therapeutic benefits can be durable, only a subset of patients respond.7, 8 In addition, unique adverse effects of immunotherapy, many of which relate to the induction of autoimmunity and pro-inflammatory-like states,10 might limit eligibility or become challenges in clinical management. Full consensus recommendations can be found on the SITC website.14 Owing to disparities in drug approval and availability in some countries, this panel focused solely on drugs approved by the FDA for the treatment of patients in the USA. Patients with high-risk stage II melanoma who are treated with interferon-α2b should have a good performance status without evidence of significant depression or psychiatric history or underlying autoimmune disease. Of these, the first nine pertain to evidence that atherosclerosis begins in childhood and that early atherosclerosis is associated with the presence and intensity of identified risk factors; it is this evidence that is reviewed here.
Except in rare circumstances, atherosclerotic disease is subclinical for the first two to three decades of life.
Atherosclerosis develops more rapidly as the number and the intensity of risk factors increase.
Finally, and most importantly, Figure 2?3 demonstrates that the absence of identified risk factors is associated with a virtual absence of advanced atherosclerotic lesions (American Heart Association Grades IV and V) in 15- to 34-year-olds. In adults, lower HDL levels are consistently shown to be associated with increased risk for CVD.
In adults, the influence of obesity on CV risk may vary by ethnicity.[73] Low SES in and of itself confers substantial risk. For risk factors such as hypertension, diabetes mellitus, obesity, and dyslipidemia, public health measures will affect prevalence, but without medical recognition and treatment, effective risk reduction cannot occur.
Many scenarios could arise in which the ethics of such a trial could be questioned, including undue exposure to risk in one of the trial arms, the discovery of novel treatments of improved efficacy during the conduct of the trial, environmental changes or shifts in priorities of the funding entity that complicate its completion, and the potential withholding of effective therapy to a generation of youths with identified risk who do not receive treatment. Many of these evidence links come from the epidemiologic studies described in this entire section and provide answers to the first nine critical questions of the evidence review: atherosclerosis begins in childhood, atherosclerosis is related to risk factors that can be identified in childhood, and the presence of these risk factors in a given child predicts an adult with risk factors. Recommendations to intervene must consider not only the relationship of the risk factor to future disease but also whether reduction of that risk factor will result in an appreciable decline in subclinical disease or in adverse clinical events with an acceptable safety profile. That this behavior is highly addictive means that the use of tobacco alone is an indication for smoking cessation counseling.
Management algorithms provide staged care recommendations for risk reduction within the pediatric care setting and identify risk factor levels requiring referral to a specialist. The childhood health maintenance visit provides a useful context for effective delivery of the CV health message. In contrast to type 1 diabetes, type 2 diabetes is highly prevalent and accounts for 90% to 95% of all diabetes cases.
The most important HbA component in diabetes is HbA1c, which has glucose attached at the N-terminal-amino groups of both ? chains of hemoglobin.
Just like glycohemoglobin, fructosamine and GA measurements serve as an index of the mean concentration of glucose in the blood during the preceding several weeks.
Portable glucose meters are routinely used either in physician offices or by patients at home.
This consensus report focuses on issues related to patient selection, toxicity management, clinical end points and sequencing or combination of therapy. An advance copy of this manuscript was submitted to the FDA for comment before submission for publication.Consensus panel and conflicts of interestPotential panel members were solicited from SITC members and non-member melanoma multidisciplinary experts, clinicians and populations in the USA expected to be affected by the development of any recommendations, including patients, patient advocates and nurses.
A conceptual model for CVD prevention by pediatric care providers beginning in childhood was developed based on the evidence review.
The studies that make up the pathways in Figure 2?2 provide evidence addressing the key questions critical to this evidence review—including associations between exposures and outcomes, efficacy of screening for conditions of interest, the presence of adverse consequences of screening, the efficacy of interventions on outcomes, and the adverse consequences of interventions.
Evidence is not adequate for the recommendations provided in these Guidelines to be specific to racial or ethnic groups or to SES.
Individuals who develop obesity have been shown to be more likely to develop hypertension or dyslipidemia as adults.[72],[94] Tracking data on physical activity are more limited.
The presence of a risk factor may confer a high relative risk of a future CV event, but intervention may not be warranted if actual event rates in the next several decades are low; conversely, a lower relative risk may be acceptable for intervention if the likelihood of an adverse event related to that risk factor is high. In contrast, recommendations to treat elevated blood pressure are based on multiple elevated measures over time because of the intrinsic variability of blood pressure and the possibility of significant modification through diet and exercise.
Rather than predicting clinical events, future research may show that a positive test signals the transition to more advanced atherosclerosis or the presence of CV target organ damage.
The Guidelines also identify specific medical conditions, such as diabetes and chronic kidney disease, which are associated with increased risk for accelerated atherosclerosis.
However, because of rapid turnover of serum proteins compared to hemoglobin, the fructosamine and GA levels reflect glucose control over a shorter period of two to three weeks rather than six to 10 weeks for glycohemoglobin. The current recommendation, therefore, is to normalize fructosamine results to a given serum albumin or total protein concentration.
Day-to-day management as guided by self-monitoring of blood glucose by patients with the use of glucose meters is a common practice today. The literature review and consensus panel voting and discussion were used to generate recommendations for the use of immunotherapy in patients with melanoma, and to assess and rate the strength of the supporting evidence. IL-2 can be considered in those patients who have a good PS and otherwise qualify for IL-2 administration as per local institutional guidelines. To provide guidance to practicing clinicians caring for patients with melanoma, SITC established a Melanoma Clinical Immunotherapy Guidelines panel (Supplementary Box 1 online). Panel members were screened for conflicts of interest using the SITC disclosure form, which mandates full financial and other disclosures including relationships with commercial entities that might reasonably be expected to have direct regulatory or commercial impact resulting from the publication of this statement.
Patients with high-risk melanoma who are enrolled in a clinical trial follow the course of treatment and treatment cessation dictated by the trial protocol.Literature review and analysisLimited data exist on the role of immunotherapy for low-risk stage II melanoma, but there have been several randomized clinical trials focusing on patients with high-risk stage II disease. This evidence inquiry is limited by the absence of reports of cost-effectiveness analyses of the screening and intervention strategies to lower CV risk in childhood. The timing and safety profile of pharmacologic interventions are important considerations for CVD prevention. Studies of subclinical atherosclerosis and LVM have been important in establishing the relationship of risk in childhood to evidence of CV injury. Recommendations for ongoing CV health management for children and adolescents with these diagnoses are provided. The office of the pediatric care provider provides an effective setting for the health care team to engage children and families in the initiation of behavior change to reduce the risk of CVD and promote lifelong CV health. Also, with a colorimetric analysis, bilirubin, hemolysis, and lipemia will likely interfere in the measurement.
There are limited data available on interferon-α2b as treatment for stage II disease.
The panel consisted of melanoma experts, including physicians, nurses and patient advocates and considered issues related to patient selection, toxicity management, treatment cessation guidelines and current recommendations for treatment sequencing with the goal of preparing a consensus statement on clinical use of tumour immunotherapy for patients with melanoma.
Disclosures of potential conflicts of interest are noted in this manuscript and in detail online.
In contrast to adult guidelines, the challenge of preparing evidence-based guidelines for CV risk reduction in childhood is augmented by the scarcity of evidence pertaining to the impact of preventive interventions on mortality, morbidity, and quality of life. The lifetime risk of disease associated with high risk in childhood may identify candidates for more aggressive intervention. The presence of multiple risk factors represents a powerful stimulus for accelerated atherosclerosis, and knowledge of this situation affects treatment decisions. Monitoring of LVM has been incorporated into treatment algorithms for hypertension in childhood.[113] However, only a few studies in the pediatric age group have used these measures as clinical end points.
Expert recommendations for how to incorporate these agents into the therapeutic approach to melanoma are provided in this consensus statement. As described throughout these Guidelines, recommended strategies for intervention should consider environmental, behavioral, physiologic, and genetic attributes, as well as the efficacy and safety of potential treatment modalities, in selecting the type and timing of any intervention and in measuring outcomes. It is expected that research using these intermediate end points will be used to clarify knowledge gaps identified in the evidence review for these Guidelines; the clinical importance of these new studies in adults and children remains to be fully established.
Tumour immunotherapy is a useful therapeutic strategy in the management of patients with melanoma and evidence-based consensus recommendations for clinical integration are provided and will be updated as warranted. Additional questionnaires were distributed after the meeting to collect further information.
In most cases individual clinical trials should be considered pending patient eligibility and interest.
The final consensus statement was made available to the entire SITC membership for open comment and these comments were considered for the final manuscript and are available in Supplementary Box 2 online.Literature reviewA search of the scientific literature (using the MEDLINE database) was conducted focusing on current therapeutic approaches in humans.
The bibliography was supplemented with additional literature identified by the panel, as appropriate. Complete tumour staging information should be assessed, including pathological features of the primary tumour and any involved lymph nodes, whole-body imaging, serum lactate dehydrogenase (LDH) levels and performance status assessment. Level A represented strong supporting evidence-based data as derived from appropriately powered prospective, randomized clinical trials and meta-analyses.
Level B represented moderate supporting data as derived from uncontrolled, prospective clinical trials.
Level C represented weak supporting data as derived from retrospective reviews and case reports.



Untreated type 2 diabetes and its complications
Nice guidelines for diabetes type 2 management
Medication errors journal of nursing bjn




Comments

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    16.04.2014

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    16.04.2014

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    16.04.2014

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    16.04.2014

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    16.04.2014