Diabetes mellitus insulin-resistant

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 ... 

Macrovascular Complications. The connection between high insulin levels (hyperinsulinemia), insulin resistance, and cardiovascular events incorrectly leads some clinicians to believe that insulin therapy may cause macrovascular complications. The UKPDS and DCCT found no differences in macrovascular outcomes with intensive insulin therapy. One study, the Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction study " reported reductions in mortality with insulin therapy. This group assessed the effect of an insulin-glucose infusion in type 2 DM patients who had experienced an acute myocardial infarction. Those randomized to insulin infusion followed by intensive insulin therapy lowered their absolute mortality risk by 11% over a mean follow-up period of approximately 3 years. This was most evident in subjects who were insulin-naive or had a low cardiovascular risk prior to the acute myocardial infarction. " ... 

There are two types of diabetes mellitus insulin dependent diabetes mellitus (IDDM, Type 1), where there is absolute deficiency of insulin and non-insulin dependent diabetes mellitus (NIDDM, Type 2), where there is insulin resistance and impaired insulin... 

J. Grimsby, Keystone Symp. Diabetes Mellitus Insulin Action Resist. Jan. 22 - 27, Breckinridge, Co. 2008, Abstract 151. 

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... 

Diabetes mellitus is a complicated, chronic disorder characterized by either insufficient insulin production by the beta cells of die pancreas or by cellular resistance to insulin. Insulin insufficiency results in elevated blood glucose levels, or hyperglycemia As a result of the disease, individuals with diabetes are at greater risk for a number of disorders, including myocardial infarction, cerebrovascular accident (stroke), blindness, kidney disease, and lower limb amputations. 

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... 

Differential diagnoses include diabetes mellitus and metabolic syndrome because patients with these conditions share several similar characteristics with Cushing s syndrome patients (e.g., obesity, hypertension, hyperlipidemia, hyperglycemia, and insulin resistance). In women, the presentations of hirsutism, menstrual abnormalities, and insulin resistance are similar to those of polycystic ovary syndrome. Cushing s syndrome can be differentiated from these conditions by identifying the classic signs and symptoms of truncal obesity, "moon faces" with facial plethora, a "buffalo hump" and supraclavicular fat pads, red-purple skin striae, and proximal muscle weakness. 

Mutations in GK (Hx IV) causes maturity-onset diabetes of the young (MOD Y), a form of non-insulin-dependent diabetes mellitus (NIDDM) characterized by onset before 25 years of age and an autosomal dominant inheritance (PI 2). This suggests that the mutations in other forms of Hx may also contribute to the development of NIDDM. Among them, Hx II is a particularly attractive candidate, although this isozyme is not expressed in red blood cells. Hx II has been analyzed extensively in the muscle of prediabetic insulin-resistant individuals. But studies have shown that Hx II mutation alone is unlikely to have a significant role in the development of peripheral insulin resistance and NIDDM (L6). 

It should be mentioned that the inhibition of superoxide overproduction and lipid peroxidation by lipoic acid has been recently shown in animal models of diabetes mellitus. The administration of LA to streptozotocin-diabetic rats suppressed the formation of lipid peroxidation products [213], In another study the supplementation of glucose-fed rats with lipoic acid suppressed aorta superoxide overproduction as well as an increase in blood pressure and insulin resistance [214]. 

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 precise mechanism involved in loss of body fat in this disorder however remains speculative but it is likely that autoimmune mechanisms (body defense mechanisms acting against body fat) are involved. Interestingly, in AGL severe insulin resistant diabetes mellitus is a typical clinical feature." Insulin resistance is frequently associated with an increased body weight and fat mass. Therefore, AGL is an interesting and unique knockout model of subcutaneous adipose tissue combined with insulin resistant diabetes mellitus. 

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 ... 

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... 

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