CLASS IV: THIAZOLIDINEDIONES
Type 2 diabetes is mainly associated with abnormalities in any of the following 3 basic pathophysiologic abnormalities:
• Impaired insulin secretion
• Excessive hepatic glucose production
• Insulin resistance in skeletal muscle, liver and adipose tissue.9
The thiazolidinediones are a unique class of agents that improve the third parameter, and are therefore also called as the “Insulin sensitizers”. Insulin resistance syndrome also called as Syndrome X is caused by a variety of pathophysiologic abnormalities mainly obesity, glucose intolerance or type II diabetes, dyslipidemia, hypertension and accelerated cardiovascular disease. All of these are basically associated with insulin resistance and compensatory
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The TZDs seem to also have advantages of prevention of cardiovascular complications of the metabolic syndrome. They have effects on the following aspects of the metabolic syndrome:
• Lowering blood pressure
• Decreasing lipid abnormalities(diabetic dyslipidemia)
• Reducing inflammatory mediators(like C reactive protein, matrix metalloproteinase -9, leukocyte counts)
• Improving pro-coagulant properties such as abnormal coagulation and fibrinolysis.10
Mechanism of action: The thiazolidinediones selectively form a ligand with the nuclear transcription factor, peroxisome proliferator –activated receptor gamma subtype (PPAR) and thus play a role in insulin resistance. Due to this unique action on insulin resistance, the TZDs can have a role in also treating non diabetic patients with insulin resistance issues.
The PPAR receptor is expressed predominantly in the liver, heart, muscle and the vascular wall. The PPAR gamma subtype receptor is expressed most abundantly in adipose tissue, pancreatic beta cells, vascular endothelium and macrophages and is mainly targeted by the TZDs.
According to clinical studies, the TZDs mainly lower fasting and postprandial glucose concentrations as well as free fatty acid concentrations. Most studies also indicated that there is a decrease in insulin concentrations. The fact that the TZDs act as insulin sensitizers has been confirmed by direct measurements in in vivo studies in humans.12
Treatment of non- diabetic
Type II Diabetes, also known as diabetes mellitus, is also called non-insulin-dependent diabetes or aadult onset diabetes. It is a medical disorder that, due to a number of factors codependent with the modern world, is characterized by higher than normal blood glucose levels that play havoc with insulin deficiency and resistance. Insulin resistance means that cells do not respond appropriately when there is free insulin in the blood system. Essentially, they body is reacting to an improper balance of sugars and insulin. Because obesity is often present, research suggests that even thought the mechanisms controling glucose and insulin are unclear, the adopose tissue likely
Diabetes can be treated in three basic ways: by diet, by diet in conjunction with tablets, or diet in conjunction with insulin. Diet serves as an initial control for non-urgent patients. If a person’s diet will have a major effect on glycaemic control, it does so reasonably quickly, within a few weeks of changing
Everybody knows that obesity is a big factor in developing type-2 diabetes, and that part of coping with this metabolic disorder is lifestyle change. If blood glucose does not go down, then medicines are introduced. Some type-2 diabetics even have to administer insulin in order to keep their blood glucose levels
Diabetes is a growing concern and health challenge for the American people (b). Diabetes is a condition in which the body cannot react to insulin appropriately or either cannot produce insulin efficiently (w). “Without a properly functioning insulin signaling system, blood glucose levels become elevated and other metabolic abnormalities occur, leading to the development of serious, disabling complications” (w). There are numerous forms of diabetes amongst the nation, however, there are three main forms of diabetes. Most people have heard of type one diabetes, type two diabetes, and gestational diabetes because they are common. Type two diabetes deals with a resistance to insulin, while
An overview of the proposed sequences of the key pathological features of type 2 diabetes is provided by Dr. Jack Leahy from the University of Vermont College Of Medicine. In his article he addresses the need for continued genetic research since little discovery has been made in this area. He also explains the known environmental causes such as sedentary lifestyles and high fat diets that contribute to type 2 diabetes, changes in lifestyle practices would reduce the incidence of this disease but this is not a practical solution. The best solution according to Dr. Leahy lays in understanding the
Type two diabetes is the most common disease today, and it has a great impact on the lives of many people in the United States. Type two diabetes results when the body is resistant to insulin or impaired secretion of insulin by the pancreatic beta cells. The pancreas produces too much insulin, but over time it is not able to make an adequate amount of insulin needed in order to move the glucose into the cells. However, there are many factors that lead to type two diabetes. They are known to be genetic, high body weight, previously identified impaired fasting glucose levels or impaired glucose tolerance, family history of diabetes, and history of gestational diabetes or delivery of a baby over 9 pounds. Type two diabetes effects about 90% to 95% of the cases of disease in the US (Hinkle & Cheever, 2013). It's
Diabetes Type 2 is a lifelong disease that develops slowly. Type 2 diabetes causes the person fat, liver and muscle cells not to respond correctly to the hormone insulin, as a result the glucose doesn’t get into these cells to be stored in energy, which causes the levels of blood sugar in the blood to increase and eventually causing damage to the nerves and small blood vessels of the eyes, kidneys and heart and lead to atherosclerosis or the hardening of the arteries which causes a heart attack or stroke. Common symptoms of diabetes type 2 is fatigue, hunger because the body can’t process the food properly so its expelled through urine, increased thirst because the person keeps peeing out everything they are consuming which makes them thirsty,
Like type one diabetes, type two diabetes both have genetic and acquired factors. Among the acquired factors obesity and physical inactivity are the leading causes. The metabolic abnormalities that lead to type two diabetes include insufficient secretes of insulin by the pancreas. Peripheral insulin resistance, and increased glucose output by the liver in the type 2 diabetes hyperglycemia develops despite the availability of insulin. Type 2 Diabetes usually manifest in adults older than forty. Type 2 Diabetes Mellitus can often be controlled by diet, exercise, and oral hyperglycemic agent (oral glucose). People with type 2 Diabetes Mellitus may or may not require insulin
Initially, the beta cells respond inadequately to hyperglycemia, resulting in chronically elevated glucose. The continuous high glucose level in the blood desensitizes the beta cells so they become less responsive to elevated glucose which in term become insulin resistance because they are then insensitive to insulin. (Linton, Adrianne Dill. (2016); Introduction to Medical-Surgical Nursing.). Type 2 Diabetes accounts for almost 90% of all diabetes. It usually onsets after the age 40, and most patients are obese. Type 2 Diabetes is based on decreased effectiveness of insulin or a relative deficit of insulin. This abnormality may involve decreased pancreatic beta cell production of insulin, increased resistance by body cells to insulin, increased production of glucose by the liver, or a combination of both factors. The treatment for Diabetes type 2 can be simply the increase in exercise and diet where as Type 1 is insulin replacement. (Karin C. VanMeter, Robert J. Hubert (2014); GOULDS PATHOPHYSIOLOGY FOR THE HEALTH PROFESSIONS, FIFTH EDITION). This type of diabetes is insidious meaning that it develops over a period of time but is also considered milder then Type
The study showed an improvement of pancreatic function, as well as an improvement in metabolic parameters, insulin levels, and insulin sensitivity.
Type 2: In type 2 diabetes, the pancreas produces insulin, however the body doesn’t respond to it as it should, this is because the quantities of the insulin being produced are insufficient, or the body’s cells just don’t react to it and so the glucose levels in the system remain high. Type 2 diabetes is a ‘progressive disease’ and can get worse if it is not managed properly. Long term effects of high blood sugar can result in heart disease or kidney
the biology side of type 2 diabetes: type 2 diabetes Unlike people with type 1 diabetes, the bodies of people with type 2 diabetes make insulin. But either their pancreas does not make enough insulin or the body cannot use the insulin well enough. This is called insulin resistance . When there isn 't enough insulin or the insulin is not used as it should be, glucose (sugar) can 't get into the body 's cells. When glucose builds up in the blood instead of going into cells, the body 's cells are not able to function properly. Other problems associated with the buildup of glucose in the blood.
Type 2 diabetes mellitus (T2DM) is a metabolic disease that is caused by insulin resistance of the peripheral tissues and impaired insulin secretion of the pancreatic β cells.1 Both conditions result in reduced glycemic control, which can lead to hyperglycemia. Despite the availability of a wide range of anti-diabetic drugs to treat T2DM,
Pharmacological interventions used to improve glucose control include both oral glucose lowering agents and injectables including glucose like peptide & insulin. Apart from insulin the choice of available pharmacological interventions to treat diabetics has expanded rapidly over the past decade. Till date, the efficacy & safety of these therapies have not been well documented in people with diabetics & CKD.
Diabetes is a systemic disease caused by a decrease in the secretion of insulin or reduced sensitivity or responsiveness to insulin by target tissue. (Beale, et al., 2011) The incidence of diabetes is growing rapidly in the United States and worldwide. An estimated 347 million people around the world are afflicted with diabetes. (Whalen, et al., 2012) According to World Health Organization (WHO), Diabetes prevalence among adults over 18 years of age has risen from 4.7% in 1980 to 8.5% in 2014. It is the major cause of blindness, kidney failure, heart attack, stroke and limbic amputation. World Health Organization (WHO) projects that diabetes will be the 7th leading cause of death in 2030. It is a complex and costly disease that can affect nearly every organ in the body and result in devastating consequences. The leading cause of non-traumatic lower extremity amputations, renal failure, and blindness in working-age adults, diabetes is also a major cause of premature mortality, stroke, cardiovascular disease, peripheral vascular disease, congenital malformations, perinatal mortality, and disability. (Cefalu, 2000) Insulin therapy and oral hypoglycemic agents have demonstrated improvement in glycaemic control. However, Insulin therapy has some disadvantages such as ineffectiveness following oral administration, short shelf life, of the need for constant refrigeration, and fatal hypoglycaemia, in the event of excess dosage.