Pathophysiology of Diabetes Mellitus Type 2

Pathophysiology of diabetes mellitus type 2 - Sixteen million people in the United States with diabetes mellitus type 2 and an additional 30-40 million with a disturbed glucose tolerance results in health care costs exceed 100 billion dollars each year. Treatment is mainly directed on microvascular complications and macrovascular. In type 1 diabetes mellitus relationship between glycemic control and microvascular complications have been upheld well. The relationship between strict glycemic control and microvascular disease in type 2 diabetes mellitus seems to be set in a prospective diabetes study recently in the United Kingdom.

Though the morbidity and mortality associated with retinopathy, nephropathy, and neuropathy, cardiovascular disease remains the leading cause of death in diabetes mellitus type 2. As a result, the treatment of the risk factors of obesity, hypertension, Hyperlipidemia and become very important and must be coordinated with good glycemic control for reduction of total mortality in diabetes mellitus type 2. Pathophysiology of diabetes mellitus type 2 - Based on the relationship between the level of glycemic control and microvascular complications as well as the contribution of hyperglycemia in the development of the disease macrovascular, it is the goal of the review is to summarize the State of knowledge at this time to provide a rational basis for treatment.

Definition of diabetes mellitus type 2, formerly known as non-insulin diabetes mellitus, recently modified by the American Diabetes Association. Several criteria can be used independently to enforce a diagnosis:

1). the oral glucose tolerance test 75 g with 2-hour value 200 mg/dL or more,
2). random plasma glucose 200 mg/dL or more with typical symptoms of diabetes, or fasting plasma glucose of
3). 126 mg/dL or more over and over. Fasting glucose values are preferred for their comfort, reproductivity, and correlation with increased risk of complications macrovascular.

The term impaired fasting glucose has been defined as fasting plasma glucose or more 110 and 125 mg/dL or less. Impaired glucose tolerance (IGT) is defined as a 2-h plasma glucose value of 140 or more and less than 200 mg/dL during oral glucose tolerance.

Individuals with impaired fasting glucose and IGT are considered at high risk for developing diabetes and macrovascular disease. Although one-third of these patients will eventually develop diabetes, dietary modification and exercise can lower the risk of the development of impaired glucose tolerance to type 2 diabetes; and may also prevent the development of IGT nondiabetes on individuals who are at high risk. Pharmacological agents can also be beneficial in limiting progression from IGT to become diabetes.

Pathophysiology of Diabetes Mellitus Type 2

Diabetes mellitus type 2 is a heterogeneous disorder with a prevalence of which varies among different ethnic groups. In the United States, the most affected population is Native American, especially in the desert Southwest, Hispanic-Americans and Asian-Americans. Pathophysiology of diabetes mellitus type 2 is characterized by peripheral insulin resistance, impaired regulation of liver glucose production, and loss of function of the β-cells, eventually causing failure of the β-cells.

A major incident is believed to be an early deficit in the secretion of insulin and, in many patients, relative insulin deficiency in relation to peripheral insulin resistance.

Β-cells
Β-cell dysfunction was initially characterized by a disturbance in the first phase of insulin secretion during stimulation of glucose and can initiate the onset glucose intolerance in diabetes type 2.

Initiation of insulin responses depends on the transmembrane transport of glucose and glucose into the glucose sensor clutch. Complex sensor glucose/glucose then induces an increase in protein and stabilizes glucokinase with damage degradation. Induction of glucokinase serves as the first step in linking the intermediary metabolism by insulin secretion apparatus. Inβ-cell glucose transport patients type 2 diabetes appears to be greatly reduced, thus shifting control point for insulin secretion from glucokinase to transport glucose (19, 20). This flaw is enhanced by sulfonylurea.

Later in the course of the disease, the second phase insulin release of the newly synthesized is compromised, the effect can be reversed, in part at least in some patients, the strict control by returning glikemia. These secondary phenomenon, called desensitization or β-cell glucotoxicity, is a result of the effect of inhibition of glucose the printed on the release of insulin and may be caused by the accumulation of glycogen in β-cells as a result of sustained hyperglycemia (23) other candidates that have been suggested are the accumulation of sorbitol in β-cell or cell-protein glycation nonenzymic-ll.

Another defect in β cell function in type 2 diabetes mellitus glucose deficiency includes damaged in response to insulin-secretagogue non-lactose, the release of insulin is asynchronous and decreased conversion of proinsulin to insulin becomes (24, 25).

The existence of a decrease in the secretion of insulin in the first phase can serve as a marker of risk for type 2 diabetes mellitus in family members of individuals with type 2 diabetes mellitus (26-30) and can be seen in patients with gestational diabetes (previously 31). However, the first phase insulin secretion disorders alone will not lead to impaired glucose tolerance.

Autoimmune pancreatic β cell damage can be a factor in a small subset of patients of type 2 diabetes and autoimmune diabetic syndrome has been called latent in adults. Pathophysiology of diabetes mellitus type 2 - This group can represent as much as 10% of patients with type 2 diabetes in Scandinavia and has been identified in the study of the United Kingdom recently, but not yet well characterized in other populations (4-6, 30).

Glucokinase is not in the β-cells in some families with a young age onset diabetes (31). However, the lack of glucokinase has not been found in other forms of type 2 diabetes (32, 33).

In a nutshell, delays on the first phase insulin secretion, although some import Diagnostics, does not seem to act independently in the pathogenesis of type 2 diabetes. In some patients with early-onset type 2 diabetes (perhaps as much as 20%) (4, 5), there may be a deficiency in the secretion of insulin that may or may not be due to autoimmune damage of β-cells and not because of a shortage of glucokinase gene. In the majority of patients with type 2 diabetes (approximately 80%), the delay in the response of insulin immediately accompanied by a phase of secondary hypersecrecy of a release of insulin as a result of congenital or acquired defects in the β cell or a compensatory response to peripheral insulin resistance. During a long period of time, perhaps years, the secretion of insulin is gradually declining, probably as a result of the accumulation of intraislet glucose metabolites. Given the decrease in β cell mass, sulfonylureas appear to serve a reduced role in the long-term management of type 2 diabetes (35). That is not answered is whether the repair of insulin resistance with early detection or insulin-enhancing drugs later will hinder the development of β-cell failure, negate or delay the need for insulin therapy.

Insulin resistance
Emanating from a demonstration by prismatic Yalow and Berson of the presence of hyperinsulinism in type 2 diabetes, insulin resistance has been considered an integral role in the pathogenesis of the disease (36). The latest critical reviews, however, have questioned virtue, specificity, and contribute to a State of insulin resistance disease (37, 38). Because insulin inhibits the secretion of chronic hyperinsulinemia (39) and (40), and hyperglycemia may damage insulin secretion response against glucose (41) as well as cellular insulin sensitivity (42, 43).), the proper relationship between glucose and insulin levels as a surrogate measure of insulin resistance has been questioned. Pathophysiology of diabetes mellitus type 2 - Type 2 diabetes patients lean over the age of 65 years has been found to be insulin sensitive as control nondiabetes those who fit the age (44). Moreover, in the majority of patients of type 2 diabetes are insulin resistant, obesity is almost always present (45, 46). Because of obesity or increased intraabdominal fat is associated with insulin resistance because of the absence of diabetes, it is believed by some that insulin resistance in type 2 diabetes is entirely caused by the coexistence of adiposity enhancement (47). In addition, insulin resistance was found in hypertension, Hyperlipidemia, and ischemic heart disease, the entity that is commonly found in association with diabetes (16, 48, 49), once again raises the question of whether insulin resistance resulting from pathogenetic disease process which is different or unique for the presence of type 2 diabetes (16, 50, 51).

Prospective studies have shown the existence of a deficiency of insulin or insulin resistance before the onset of type 2 diabetes (48). Two studies have reported the presence of insulin resistance on relative nondiabetes from diabetic patients at a time when they are still normal glucose tolerance (52, 53). In addition, relatives of the first level of the patients with type 2 diabetes have been found to have a disruption of insulin on the synthesis of skeletal muscle glycogen since both lower stimulation of tyrosine kinase activity of insulin receptors and activities of synthase Glycogen decreased (54, 55).). Other studies on this high-risk group had failed to demonstrate the insulin resistance, and in the same group, early phase insulin release distraction and loss of normal patterns of the oscillator of a release of insulin have been described (56, 57). Based on these different research, it is still not possible to separate the insulin deficiency of insulin resistance in the pathogenesis of type 2 diabetes. However, the two entities that expressly contributed to the disease that is already established.

Hearts
The ability of insulin to suppress glucose production in the State either hear fasting and postprandial is normal on the first level of the family of type 2 diabetic patients (26). This is an increase in postprandial glucose production rates that marked the evolution of IGT (52). Finally, both the production of glucose fasting and postprandial rise as type 2 diabetes progresses. Hepar insulin resistance characterized by decreased activity glucokinase and increased conversion of the substrate into glucose even though there is insulin (53). Pathophysiology of diabetes mellitus type 2 - Thus, the heart in diabetes type 2 is programmed to produce excess and deficiency of glucose. Increased levels of free fatty acids that are found in type 2 diabetes can also play a role in hepatic glucose production increased (50). In addition, the latest evidence suggests an important role for the kidney in the production of glucose through gluconeogenesis, uncontrolled in the presence of type 2 diabetes (58).