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Search and download new Rapidshare, Megaupload, Music, MP3, Movie, Video, serial, hdrip, 720p,Torrent, CDKey, 2014, HD, 2015 absolutely for free. Although its main physiological abnormalities are insulin resistance and impaired insulin secretion, the specific underlying determinants of these metabolic defects remain uncertain. There are complex interactions between genetic, epigenetic, environmental and behavioral factors that contribute to the development of diabetes.
Non-pharmacological and pharmacological interventions have been used for diabetic management. The Asociación Latinoamericana de Diabetes (Latin American Diabetes Association, ALAD) brought together medical associations in 17 countries in Latin America to produce a consensus statement regarding the treatment of type 2 diabetes. Over the past few years, research has started to focus on the use of novel adjuvant drugs as antioxidants and anti-inflammatory drugs for better management, as it was revealed that both oxidative stress and inflammation play a critical role in the disease pathogenesis.
The goal of the document is to provide practical recommendations that will guide clinicians through a simple decision-making process for managing patients. Thus, the development of antidiabetic drugs that can reverse insulin resistance is a potential therapeutic target.
The cornerstone elements for therapeutic decision making are: severity of hyperglycemia, clinical condition of the patient (stable or with metabolic decompensation), and body mass index.
Although antidiabetic drugs may be effective in improving glycemic control, they do not appear to be effective in entirely preventing the progression of pancreatic AY-cells damage mediated by chronic hyperglycemia-induced decline in intracellular antioxidants. The algorithm is based on the scientific recommendations of the 2006 ALAD guidelines (a document prepared using an evidence-based approach) and data from recent randomized controlled studies. Diabetes and other chronic, non-transmissible diseases are now the leading health problems. Despite the large and growing number of diabetes cases, this geographic area invests limited financial resources in diabetes care. In the year 2000, the direct cost of diabetes care in Latin America and the Caribbean was approximately US$ 10 billion; minimal when compared to the indirect cost of about US$ 55 billion resulting from disease-related consequences. Most private health insurance plans cover medical assistance, procedures, and hospitalization, but not medication (2-5).
The burden of disease will be even greater in the coming years because the population has a large proportion of young adults living in urban areas and engaged in unhealthy lifestyles. Thus, the impact of diabetes in Latin America is growing fast and the national health systems are unprepared. Such restructuring should be based on the best available clinical evidence, but existing international guidelines should be adapted to reflect the differences and needs of each geographic area.
The unique challenges regarding type 2 diabetes treatment in Latin America are a result of the interactions among the area's socioeconomic factors, its variety of cultures and traditions, and its limited health resources. Consensus documents and practice guidelines that are specifically oriented toward the Latin American environment are needed to train and guide primary care physicians.
In line with its commission, ALAD called upon leaders and representatives from the endocrine and diabetes associations of 17 countries in Latin America to produce a consensus statement for the treatment of type 2 diabetes mellitus. The participants were divided into three groups; each group discussed and responded to three of the nine questions addressed by the present report.
A writing committee prepared the summary, which was approved by all of the endorsing associations' representatives.
The final version of the document was prepared and approved by the members of the writing committee. The algorithm was based on the scientific recommendations of the 2006 ALAD guidelines-a document prepared using an evidence-based approach (6)-and data from recent randomized controlled studies. Also included in this algorithm were the possible clinical scenarios diabetes patients may present and the necessary actions to follow in each case.
Additionally, two groups of patients-divided according to the level of glycemic control and clinical condition-are included: Group 1. These patients constitute a therapeutic challenge; primary care units do not have the resources to manage such cases.
Without a multidisciplinary approach and adequately informed medical personnel, patients, and relatives, obese patients with diabetes frequently continue gaining weight and do not achieve treatment goals.
The section on obesity emphasizes the importance of helping patients follow a healthy lifestyle before and during the escalation of pharmacological treatment. In type 2 diabetes, the Kumamoto study (7) and the United Kingdom Prospective Diabetes Study (UKPDS) (8, 9) demonstrated significant reductions in microvascular and neuropathic complications with intensive therapy.
Similar to the Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCTEDIC) studies' findings (10), long-term follow-up of the UKPDS cohort has recently demonstrated a "legacy effect" of early, intensive glycemic control on long-term rates of microvascular complications. This benefit continues, even if the differences in glycemic control between the intensive and standard cohorts are lost after the end of the study (10, 11).
In Latin America, fasting blood glucose (venous or capillary) values are the key elements used by physicians to evaluate their patients and guide decisions.
However, in line with other scientific organizations (12-14), glycosylated hemoglobin (HbA1c) is recommended as the optimal method to assess glycemic control.
As shown in Table 1, A1c levels can be translated to mean plasma glucose concentrations, making it easier for patients to understand the information. In several large, randomized, prospective clinical trials, treatment regimens that reduced A1C < 7% were associated with fewer long-term microvascular complications. Whereas many studies and meta-analyses (15-17) have shown a direct relationship between A1C and the incidence of cardiovascular events, the potential of intensive glycemic control to reduce cardiovascular mortality has been less clearly defined.
Based on current clinical evidence (18-21), an HbA1c < 7% is recommended as the most appropriate level for the majority of patients. In addition, this Consensus highlights plasma lipid and blood pressure goals as prominent objectives of diabetes management (Table 2). Several controlled studies and meta-analyses have shown the benefits of lipid lowering therapies in patients with diabetes.
The concentration of microalbuminuria should be measured annually in all type 2 diabetes patients and in type 1 diabetes patients with disease duration > 5 years. Microalbuminuria should be treated by achieving blood pressure targets; the use of angiotensinconverting enzyme (ACE) inhibitors inhibitors and angiotensin II receptor blockers have been shown to delay the progression to macroalbuminuria. Drugs currently used in diabetic care, including mean and maximum doses are described in Table 4. The pharmacological characteristics of insulin preparation and insulin analogues are included in Table 5.

Besides its therapeutic effects, Metformin has been shown to decrease cardiovascular complications in retrospective (22, 23) and prospective analyses (8, 9) and has the advantage of being easily accessible for virtually all populations. The eGFR can be estimated by using the Cockcroft-Gault formula (24) or the MRDS equation used in the Diet in Renal Disease Study-recommended by the National Kidney Disease Education Program (United States, 25). However, the risk of hypoglycemia (especially with first generation, long-acting sulfonylureas) and weight gain should be considered (28). The efficacy of sulfonylureas over the longterm is less than that of Metformin and glitazones. Due to their short half-life, meglitinides can be used in patients with renal failure (29). Patients should be carefully selected for this therapeutic option in order to reduce the risk of heart failure, coronary events, or fractures (particularly in postmenopausal women) (30). Gliptins are orally active, safe, and highly tolerable, with a minimal risk for hypoglycemic events. These drugs have been used in combination with Metformin, sulfonylureas, and thiazolidinediones. However, additional evidence is required to assess the long-term effects of the DPP-IV inhibitors, in particular issues such as safety and their effectiveness in the prevention of the diabetes-related chronic complications (32).
The decision should be based on cost-effectiveness analysis and individualized patient care. Other options based on Metformin may also be considered at this stage: Metformin + Meglitinides, Metformin + Glitazones, Metformin + DPP-4 inhibitors, and Metformin + Incretin Analogues (6, 28, 35, 36). Options include the use of DPP-IV inhibitors, GLP-1 analogue, or glitazones, in addition to Metformin and a sulfonylurea. The intervention of a diabetes specialist could be considered in patients who are not reaching the treatment targets despite the use of three agents. What should be done to manage overweight patients not controlled by monotherapy and who continue to gain weight? These patients require closer monitoring and the support of a multidisciplinary team, if available, for the implementation of an adequate dietary plan, an exercise program, and psychological support.
The use of combination therapy that may provoke weight gain should be limited to cases that remain hyperglycemic despite lifestyle modifications.
The timeframe for considering combination therapy will depend on the patient's circumstances (39). This is due to the progressive decline in insulin secretory capacity that occurs in type 2 diabetes. Initially, control can be achieved with a bedtime dose of Neutral Protamine Hagedorn (NPH) insulin or a long-acting insulin analogue (Glargine or Detemir) in combination with oral agents.
The frequency of the adjustments depends on the patient characteristics and the experience of the practitioner.
Changes in the dosage on a daily basis may be necessary in severely hyperglycemic patients. When the treatment goals are close to being achieved, it is better to adjust the amount of insulin every 3-4 days.
A time period of at least 1-3 months is recommended to assess whether treatment goals are achieved before considering a change in treatment regime.
Of note, the combination of insulin with glitazones is not recommended due to the increased risk of edema and heart failure. The choice depends on insulin availability, patient requirements, metabolic behavior, and risk of hypoglycemia. One option is a mixture of 2 types of insulin, such as regular insulin and NPH insulin, or a combination of a short acting insulin analogue (Lispro, Aspart, or Glulisine) with NPH insulin.
Another option is 1-2 doses of a long-acting analogue (Glargine or Detemir) with a dose of regular human insulin or a rapid-acting insulin analogue before each meal.
Time of action, peak activity, and duration of different insulins and insulin analogues are shown in Table 5 (40, 41).
At this stage of intensive insulin therapy, referral of the patient to a specialist is recommended. If there is a lack of response after a 1-3 month period, patients should be started on an insulin regimen (42). Any of the insulin regimens described above is useful for the prompt correction of hyperglycemia and nutritional status (43).
Later, once these patients are stable and have regained weight, the treatment should be reassessed; the possibility of switching to oral drugs can be considered. Some cases may be eligible for a more intensive therapeutic regimen with multiple insulin doses or an insulin pump. It is assumed that measures for adopting a healthy lifestyle are in place and reinforced regularly.
All therapeutic alternatives should be given a reasonable amount of time to evaluate their maximal efficacy.
This is especially relevant if there is clinical improvement, weight stabilization, and gradual improvement of fasting and post-prandial glucose and HbA1c values.
Primary care physicians are discouraged from delaying the addition of an oral glucose-lowering agent or insulin. Clinical inertia is a contributing factor for not achieving treatment targets in all health systems. In most countries, the primary care physician is responsible for the treatment of a large proportion of the diabetic population. Self-monitoring is a fundamental tool for all patients with diabetes; in particular, those on insulin treatment who require intensive glucose monitoring. It helps determine whether patients are on the right track for achieving treatment objectives (44).
Capillary glucose measurement has become more accessible in Latin America; however, the high cost of glucometers and test strips is still a significant problem for many patients. It must be taken into account, however, that this index is not readily available throughout Latin America, and where it is available, cost is often a deterrent. General practitioners are often responsible for making treatment decisions during the early stages of the disease. However, it is essential that practitioners aim to achieve the standards of diabetes care in their patients.

Continuing medical education for primary care physicians must be a priority for national and international medical institutes. Patients who do not achieve treatment goals within a 6-12 month period should be referred to a specialist. Training of medical students and primary care physicians should be updated to provide the necessary skills for successfully implementing diabetes care and promoting long-term adherence to therapy (45). In addition, diabetes education programs are needed for both patients and the general public. If these actions are not implemented, a large percentage of the diabetic population will remain outside of the treatment target levels (45, 46). They can prepare position documents that guide doctors in achieving better therapeutic results.
Latin American countries share many ethnic, social, cultural, and lifestyle characteristics.
As such, ALAD has produced specific recommendations for Latin America for the last 40 years. This document was approved and recommended by the Pan American Health Organization (PAHO) as guidelines for Latin America (49).
The aim was to integrate the ALAD guidelines with important information from each organization to produce a common standard for diabetes in Latin America.
The recommendations are applicable to practically every patient, with some possible exceptions. Acknowledges the importance of reaching treatment targets early, especially in the initial years of the disease. Includes special notes regarding obese patients who are unable to reach glucose treatment goals and continue to gain weight. Recommends the early use of combination therapy and the timely addition of insulin in patients who do not achieve adequate glucose control.
Primary care physicians are discouraged from delaying the addition of an oral glucose lowering agent or insulin because this practice results in prolonged exposure to the adverse effects of hyperglycemia. Describes clinical traits of the available glucose-lowering agents to aid in selecting from among the treatment options. Recognizes that, in Latin America, logistics can limit the use HbA1c determination-the gold standard for glycemic control-and offers regular determination of venous and capillary glycemia as an acceptable alternative.
The position statement recommends treatment targets for both HbA1c and fasting glucose levels. In addition, the importance of individual practitioners as providers of diabetes care in Latin America is highlighted. Provides clinical indications and possible contraindications for all of the existing glucose lowering agents. It is the responsibility of each medical institute and ALAD to educate physicians to ensure correct medication usage.
Because this consensus takes into account the unique challenges faced by patients and physicians in Latin America, its strategies are more feasible and it is hoped that its impact will go farther than that of past efforts to improve diabetes management. Special emphasis is given to the management of the obese patient with type 2 diabetes not reaching the treatment targets. With the help of all participating institutions, we expect that this consensus document will be helpful to improving the quality of diabetes care in Latin America. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complication in patients with type 2 diabetes.
Effect of intensive blood glucose control with Metformin on complication in overweight patients with type 2 diabetes.
Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: meta-analysis of randomized trials.
Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Decreased mortality associated with the use of Metformin compared with sulfonylurea monotherapy in type 2 diabetes.
Reduced cardiovascular morbidity and mortality associated with Metformin use in subjects with type 2 diabetes. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOPNIDDM Trial.
Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in patients with type 2 diabetes treated with metfomin and a sulfonylurea. Effects of exenatide on glycemic control and weight over 30 weeks in Metformin-treated patients with type 2 diabetes.
PRESERVE-B: two year efficacy and safety of initial combination therapy with nateglinide or glyburide plus Metformin. Effect of Metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus. Weight loss reverses secondary failure of oral hypoglycaemic agents in obese non-insulin-dependent diabetic patients independently of the duration of the disease. Approaches to treatment of pre-diabetes and obesity and promising new approaches to type 2 diabetes.
Self monitoring of blood glucose in patients with type 2 diabetes who are not using insulin: a systematic review.
A Multi-Center, Epidemiologic Survey of the Current Medical Practice of General Practitioners Treating Subjets with type 2 Diabetes Mellitus In Latin America.
Nathan DM, Buse JB, Davidson MB, American Diabetes Association, European Association for the Study of Diabetes.

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