Diabetes mellitus type insulin resistance

Diabetes mellitus is a disorder of carbohydrate metabolism characterized by excessive thirst and excretion of abnormally large quantities of urine containing an excess of sugar, caused by a deficiency of insulin. Patients with Type 1 diabetes mellitus depend on external insulin (most commonly injected) for their survival because the hormone is no longer produced internally Patients with Type 2 diabetes mellitus are insulin resistant, and because ofsuch resistance, may suffer from a relative insulin deficiency. Some patients with Type 2 diabetes may eventually require insulin if other medications fail to adequately control blood sugar levels. 

T Diabetes mellitus, caused by a deficiency in the secretion or action of insulin, is a relatively common disease nearly 6% of the United States population shows some degree of abnormality in glucose metabolism that is indicative of diabetes or a tendency toward the condition. There are two major clinical classes of diabetes mellitus type I diabetes, or insulin-dependent diabetes mellitus (IDDM), and type II diabetes, or non-insulin-dependent diabetes mellitus (NIDDM), also called insulin-resistant diabetes. 

Type 2 Diabetes Mellitus This is the most prevalent form of diabetes and is characterized by both an insulin secretion defect and insulin resistance. Maturity-onset diabetes of the young (MODY), attributable to mutations of the glucose kinase gene (discussed earlier), may also be classified as type 2 diabetes mellitus. Obesity is a contributory factor and may predispose to insulin resistance with eventual development of type 2 diabetes mellitus. The precise mechanism by which obesity leads to insulin resistance in the target tissues is not understood. However, in several animal models (e.g., ob/ob mouse, db/db mouse) mutations have been identified that cause both obesity and diabetes mellitus. Unlike type 1 diabetes mellitus, type 2 is not an autoimmune disease. Studies with monozygotic twins have revealed a 90% concordance rate for type 2 diabetes mellitus, suggesting the involvement of genetic factors in the development of the disease. 

Diabetes mellitus An endocrine disease characterized by an elevated blood glucose concentration. There are two major forms of diabetes mellitus type I, or insulin-dependent, and type 11, or non-insnlin-dependent. Type I is cansed by a severe lack or complete absence of insnlin. Type II is caused by resistance to insnlin, that is, an inability to respond to physiologic concentrations of insnlin. 

Diabetes mellitus is defined as hyperglycaemia (fasting > 7 mM and/or 2 h postprandial >11.1 mM) due to absolute or relative lack of insulin. The most common forms are type 1 diabetes (prevalence 0.25%), with absolute lack of insulin, and type 2 diabetes (prevalence 4-6%) which is due to the combination of insulin resistance and insufficient insulin secretion. 

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

The entry rate of glucose into red blood cells is far greater than would be calculated for simple diffusion. Rather, it is an example of facilitated diffiision (Chapter 41). The specific protein involved in this process is called the glucose transporter or glucose permease. Some of its properties are summarized in Table 52-3-The process of entry of glucose into red blood cells is of major importance because it is the major fuel supply for these cells. About seven different but related glucose transporters have been isolated from various tissues unlike the red cell transporter, some of these are insidin-dependent (eg, in muscle and adipose tissue). There is considerable interest in the latter types of transporter because defects in their recruitment from intracellular sites to the surface of skeletal muscle cells may help explain the insulin resistance displayed by patients with type 2 diabetes mellitus. 

CF-related diabetes shares characteristics of both type 1 and type 2 diabetes mellitus but is categorized separately. The primary cause of CFRD is insulin deficiency resulting from both reduced functional pancreatic islet cells and increased islet amyloid deposition. Insulin secretion is delayed in response to glucose challenge, and absolute insulin secretion over time is reduced. Some insulin resistance may also be present in CFRD however, sensitivity may be increased in CF patients without diabetes.8... 

Type 2 Peripheral tissue resistance to the action of insulin Insulin secretory defects Includes those formerly classified as adult onset diabetes, type II DM or non-insulin dependent diabetes mellitus (NIDDM). Ketosis is rare. 

In patients with type 1 insulin-dependent diabetes mellitus not adequately treated with insulin, fatty add release from adipose tissue and ketone synthesis in the liver exceed the ability of other tissues to metabolize them, and a profound, life-threatening ketoaddosis may ocxnir. An infection or trauma (causing an increase in cortisol or epinephrine) may predpitate an episode of ketoaddosis. Patients with type 2 non-insulin-dependent diabetes meUitus (NIDDM) are much less likely to show ketoaddosis. The basis for this observation is not completely understood, although type 2 disease has a much slower, insidious onset, and insulin resistance in the periphery is usually not complete. Type 2 diabetics can develop ketoacidosis after an infection or trauma. In certain populations with NIDDM, ketoaddosis is much more common than previously appredated. 

A brief overview about the fundamental principles of the pathogenesis of skeletal muscle insulin resistance and its contribution to the development of type 2 diabetes mellitus is given in the following. Priority is given to the role of lipid metabolism, which is the main field of the reported spectroscopic studies. Furthermore, the technique of euglycemic hyperinsulinemic glucose clamp is described allowing determination of the individual insulin sensitivity of musculature. The role of IMCL in insulin resistance of the skeletal muscle is discussed. 

The prevalence of Type 2 Diabetes (T2D) is increasing world-wide and considered one of the main threats to human health in the 21st century. In 2010, 221 million patients are expected to be diabetic (compared to 151 million in the year 2000). The increase in diabetes prevalence is considered to be secondary to changes in human lifestyle accompanied by physical inactivity and unlimited food supply. Skeletal muscle insulin resistance, defined as the reduced response of skeletal muscle to a given dose of insulin, is a common finding in patients with type 2 diabetes mellitus and can be found before the onset and predict the development of the disease. Several factors determine skeletal muscle insulin sensitivity and among others alterations in fatty acid metabolism have been proposed. ... 

To gain further insight into the mechanisms involved in defective insulin-stimulated glucose uptake in skeletal muscle of insulin-resistant subjects, the possible role of IMCL in the pathogenesis of skeletal muscle insulin resistance and type 2 diabetes mellitus was explored by comparing insulin sensitivity (GIR) and IMCL content of insulin-resistant and insulin-sensitive offsprings of patients with type 2 diabetes. Twenty-six healthy subjects were included in the first study, 13 of them classified as insulin-sensitive and further 13 as insulin-resistant. Metabolic and anthropometric data are given in Table 4. 

The insulin resistance that is the hallmark of type 2 diabetes mellitus is thought to arise from multiple factors. Of the putative contributing factors listed below, which is likely to be the most direct contributor to the disease ... 

In the case of NIDDM (maturity onset or type II diabetes mellitus), insulin is present in the blood at normal (or even elevated) levels, but fails to promote any of its characteristic effects. A number of factors can contribute to such insulin resistance, including ... 

Oral antidiabetic agents might be indicated in noninsulin dependent diabetes mellitus (NIDDM), i.e. diabetes Type II where insulin resistance caused by down-regulation of insulin receptors or a failure of the pancreas to release insulin even though it is formed, play a role. However, oral antidiabetic... 

Diabetes mellitus is characterized by hypergly-caemia and disturbances of carbohydrate, fat and protein metabolism that are associated with absolute or relative deticiencies in insulin action and/or insulin secretion. Although diabetes is an endocrine deficiency or resistance state its major manifestations are those of metabolic disease with wide ranging tissue effects. Insulin resistance does exist in type 2 diabetes, however it is also exists in many individuals without diabetes. It is difficult to accept insulin resistance is the sole determining pathogenic factor in type 2 diabetes. Therefore, it is more appropriate to describe type 2 diabetes as a condition of /3-cell dysfunction in an insulin resistance background. 

Diabetes mellitus has been traditionally classified into insulin-dependent diabetes mellitus (IDDM), also known as type I (formerly called juvenile-onset diabetes mellitus), and non-insulin-dependent diabetes mellitus (NIDDM), also known as type II (formerly referred to as adult-onset diabetes mellitus). There are clearly varying degrees of overlap, and though it is often important to know whether a particular individual possesses relative insulin deficiency or relative insulin resistance or both, some of the more salient differences between IDDM and NIDDM are summarized in Table 67.1. 

The sulfonylureas are ineffective for the management of type I and severe type II diabetes mellitus, since the number of viable -cells in these forms of diabetes is small. Severely obese diabetics often respond poorly to the sulfonylureas, possibly because of the insulin resistance that often accompanies obesity. 

Low LPL activity can also be found secondary to metabolic dysregulation, notably in insulin resistance and type 2 diabetes mellitus. In fact, diabetic hypertriglyceridemia is caused in part by decreased LPL secretion in response to reduced insulin action. Another preanalytical pitfall results from the high affinity of LPL for triglyceride-rich lipoproteins. When extremely hypertriglyceridemic plasma is prepared by cen-... 

The metabolic abnormalities of type 2 diabetes mellitus are the result of insulin resistance expressed primarily in liver, muscle, and adipose tissue (Figure 25.10). 

Schofl C, Liibben G. Postmarketing surveillance study of the efficacy and tolerability of pioglitazone in insulin-resistant patents with type 2 diabetes mellitus in general practice. Clin Drug Invest 2003 23 725-34. 

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