Last Updated 06 Jul 2020

A Systematic Review on the Comparison of Avandia and Actos in Treatment of Type 2 Diabetes Mellitus

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Type 2 diabetes mellitus is a condition that is characterized by a chronic rise in the glucose levels of the blood.  It can lead to changes of the blood vessels of the retina, nephron, heart, nerves, etc, causing a lot of complications.

Individuals, who suffer from type 2 diabetes, may or may not require insulin (as the condition primarily occurs due to insulin resistance or improper utilization of insulin by the blood cells).  In many cases, people who suffer from type 2 diabetes, are ultimately given insulin, even though the drug is not very effective in control the high blood sugar levels (Ligaray, 2008).

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Studies conducted in the UK effectively demonstrate that 25 % of the patients who suffer from type II diabetes require insulin within 6 years of initiating therapy with oral hypoglycaemic agents (Edelman, 2005).

In clinical practice, type 2 diabetes mellitus is one of the commonest diseases that are seen.  The insulin levels may be low, defective in nature or the very utilisation of insulin by the fat, liver and the muscle cells may be hampered.  The individual may not depend on insulin for bringing back the blood glucose levels back to normal.  Ketosis seldom develops, but is common under stressful conditions (Inzucchi, 2007).

Today, in the US, the screening for diabetes is usually performed in elders or high-risk individuals, and as such there may be several members of the general population who may be silently suffering from the disorder.

The prevalence of diabetes mellitus in the US is about 7 %, but in individuals above the age of 50 years, the incidence may be about 15 %.  Certain minority groups including the Hipics, African-Americans, Native Americans, etc, are at a higher risk of developing the disorder.

  The mean age of incidence of the disorder in high-risk populations usually occur at a younger age compared to the White American populations.  If we look at the prevalence of diabetes mellitus type 2 throughout the world, the incidence is high in Indians, Polynesians, Micronesians, Latin Americans, etc.

In Australians, Africans, Aborigines, Asians, etc, the incidence is relative lower when they live in the native countries.  However, when they migrate to the US, the prevalence of the disorder is relatively higher, owing to the change in lifestyle, poor control over risk factors, etc.

A great proportion of diabetic patients die from cardiac diseases such as heart attacks, stroke, etc.  Studies have effectively demonstrated that the risk for cardiac disease raises two-folds in men, and up to four folds in women (Ligaray, 2008).

The main pathophysiology of diabetes is the rise in the blood glucose levels (hyperglycaemia) due to the low insulin levels in the blood, improper utilisation of insulin by the cells, defective functioning of the insulin or resistance to insulin.  The pancreatic beta islet cells may not produce sufficient amounts of insulin required by the body or several groups of cells present in the body such as the fat, muscle, liver, etc, may be resistant to the action of insulin.

Studies conducted during autopsy have effectively demonstrated that the beta cell mass in type 2 diabetics are reduced to about half the normal size.  The body cells find it seemingly difficult to utilize glucose resulting in lower amount of glucose transportation to the muscles, greater production of glucose by the liver and greater breakdown of fat (Ligaray, 2008).

Other causes of diabetes type 2 include production of substance by the body that hamper the action of insulin, glucotoxicity and lipotoxicity.  When the individual consumes carbohydrates, there are chances that the blood glucose level would raise further, as insulin is not available to control (Inzucchi, 2007).

The ability of the body to use insulin immediately to control carbohydrate and sugar level following ingestion is difficult (Ligaray, 2008).  Studies may have shown that although the insulin deficiency may be mild, the ability of the insulin to stop an immediate rise in the blood glucose level would be absent.  When the individual suffers from mild type 2 diabetes during the initial stages, there are chances that the insulin secretion would respond to other secretogogues such as amino acids.

However, in severe type 2 diabetes, the condition does not respond to other secretogogues resulting in a severe deficiency of insulin.  In individuals suffering from type 2 diabetes, there may be deposition of an amyeloid-like substance in the beta-cells of the pancreatic islets.  The beta-cells begin to malfunction following the deposition of amyloid (Inzucchi, 2007).

In some of the type 2 diabetics the insulin secretion may be defective in nature.  The ability of the cells to respond to insulin is reduced and the normal response is less.

The cells may not be able to use the insulin effectively to ensure utilization of glucose by the cells.  In an environment of hyperglycaemia, the cells find it very difficult to utilize the insulin and the glucose.  The body finds it difficult to produce glycogen from glucose in the liver and breakdown of fats, as a result of the decreased sensitivity of the insulin.

The exact reason for the poor response of the cells to insulin is not understood clearly, but scientists suggest that it has to do with the defective mitochondrial functioning and the accumulation of free fatty acids in the cells that are usually supposed to respond to insulin.  The insulin receptors in such cells may be normal, but the insulin pathways that are related to the insulin receptors may go haywire.

The functioning of the glucose transporting agent GLUT may become abnormal.  Scientists also feel that the defects in insulin use and glucose transportation may be due to a genetic defect.  Obesity also increases the risk of the individual developing resistance to insulin.  The presence of free fatty acids in the body would suggest greater amount of lipid deposition in the liver and the muscles thus playing a major role in developing insulin resistance (Inzucchi, 2007).

When the blood glucose levels are high, the sensitivity of the cell to insulin and the ability of the cell to utilize glucose are seriously affected.  Besides, a rise in the lipids in the blood can affect glucose metabolism, causing a raise in hepatic gluconeogenesis, and raising the free fatty acid levels.  The pancreas functions abnormally and the muscles are unable to utilize glucose effectively (Inzucchi, 2007).

It may be difficult to assert whether the primary defect in type 2 diabetics is due to insulin insufficiency or insulin resistance.  Studies have demonstrated that in high-risk populations, the initial defect is primarily due to insulin resistance and a decrease in the insulin sensitivity.

However, diabetes would not occur only with insulin resistance alone.  Studies have shown that frequently due to the secretory defects, the beta cells seem to get exhausted.  It may also be that chronic stimulation of the beta-cells along with the genetic defects would result in insulin insufficiency (Inzucchi, 2007).

Evidence strongly supports that genetics and environmental factors both play a major role in the development of diabetes mellitus type 2 (some even suggest complex genetic factors).  Most of the forms of type 2 diabetes mellitus have been polygenic in nature, whereas maturity-onset diabetes of the young (MODY) has been monogenic in nature.  There is a clear familial linkage seen in diabetes mellitus type 2, but there seems to be no classical Mendelian inheritance (Inzucchi, 2007).

Diabetes mellitus patients are at the risk of high mortality in case their condition worsens and complications develop.  Hence, one the keys to ensure a longer lifep in diabetes patients is effective management using drugs and medications.

Studies have clearly demonstrated that diabetes patients require an aggressive, intensive and early intervention that would be able to identify a rise in the blood sugar level and ensure that it is brought within normal range.  One of the most difficult complications of diabetes patients would be developing is heart disease.

The mortality from heart disease is quite high (70 %) in diabetics.  Besides, the costs of managing a patient suffering from diabetes and heart disease are about three times higher (Unger, 2008).

Diabetes mellitus is mainly diagnosed on the basis of the plasma glucose levels.  The fasting blood glucose level should be more than 126 mg per dl of blood.  The post prandial blood glucose level should be greater than 200 mg per dl of blood (typically taken 2 hours after a meal).  The impaired glucose tolerance levels include 140 to 199 post-prandially.

In diabetes, a random blood glucose test should demonstrate reading above 200 mg per dl along with the presence of symptoms of diabetes.  For the individual to be classified as diabetic, the blood glucose tests should demonstrate consistent results.  Haemoglobin A-1c is also useful in demonstrating the retrospective glucose levels, but cannot be taken as standard as there are several potential errors that may be associated with this test (Buse, 2008).

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