Diabetes mellitus type lipid metabolism

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. 

Diabetes mellitus is a very common metabolic disease that is caused by absolute or relative insulin deficiency. The lack of this peptide hormone (see p. 76) mainly affects carbohydrate and lipid metabolism. Diabetes mellitus occurs in two forms. In type 1 diabetes (insulin-dependent diabetes mellitus, IDDM), the insulin-forming cells are destroyed in young individuals by an autoimmune reaction. The less severe type 2 diabetes (non-insulin-dependent diabetes mellitus, NIDDM) usually has its first onset in elderly individuals. The causes have not yet been explained in detail in this type. 

Diabetes mellitus is a heterogeneous group of disorders characterized by abnormalities in carbohydrate, protein, and lipid metabolism. The central disturbance in diabetes mellitus is an abnormality in insulin production or action or both, although other factors can be involved. Hyperglycemia is a common end point for all types of diabetes mellitus and is the parameter that is measured to evaluate and manage the efficacy of diabetes therapy. 

However, very low plasma levels of HDL cholesterol are also found in patients with genetically disturbed metabolic pathways that are indirectly linked to HDL metabolism. For example, many patients with lipid storage diseases like Gaucher s disease (glucocerobrosidase deficiency, OMIM 230800-231000), Nieman-Pick disease types A or (sphingomyelinase deficiency, OMIM 257200 and 607616, respectively), Niemann-Pick disease type C (OMIM 257220), hypertriglyceridemia, or diabetes mellitus present with low HDL cholesterol [22]. 

Loop and thiazide diuretics may also impair glucose and lipid metabolism, and it has been suggested that high doses of these agents may predispose some patients to type 2 diabetes mellitus.1,13 Although the exact risk of such metabolic disturbances is not known, the long-term use of these drugs has been questioned.67 Nonetheless, concerns about metabolic side effects can be minimized if low doses are administered.13... 

Although it is not exactly clear how much these agents can reduce the risk of a major cardiac event (e.g., infarction, stroke), these drugs will probably remain the first choice for people with certain hyper-lipidemias (e.g., increased triglycerides). These drugs are likewise advocated for mixed hyperlipidemias that are common in metabolic disorders such as type 2 diabetes mellitus (see Chapter 32).32,141 Certain fibrates can be used with other drugs, such as statins, to provide more comprehensive pharmacologic control of certain lipid disorders.30,147... 

Rosmond and Bjorntorp also addressed the potential effect of HPA axis activity on established anthropometric, metabolic, and hemodynamic risk factors for cardiovascular disease, type 2 diabetes mellitus, and stroke [112], Strong and consistent correlations were found not only within but also between different clusters of risk factors, including lipid profiles [110]. The close association to HPA axis abnormality may explain the previously reported powerful risk indication of abdominal obesity for the diseases mentioned under environmental stress challenges [112]. 

In another research article, Wang et al. [20] successfully applied LC-MS metabonomic techniques to the metabolite profiling of plasma phospholipids in type 2 diabetes mellitus (DM2) patients. Diabetes mellitus is associated with a metabolic disorder of lipid or fatty acid in phospholipids. The authors were not only able to differentiate between the samples from the DM2 patients and the healthy subjects but also identified a number of phospholipid molecular species that could be used as potential biomarkers for a differentiation of DM2 patients from the healthy individuals and perhaps even an early detection of DM2. 

Despite its proven benefit in the control of blood glucose, PPARy agonists have been associated with an increased incidence of myocardial infarction and death from cardiovascular causes [71]. Numerous companies are therefore working actively on specific PPARa modulators, and a number of discovery and preclinical programs have been initiated with the aim of improving potency and selectivity compared to the fibrates. PPARa-selective compounds that are currently under development are shown in Figure 13.9. With the exception of K-lll (for a recent review, see Ref. [72]), which is developed for the treatment of type 2 diabetes mellitus, the development of all known PPARa activators is focused on lipid metabolism. 

Diabetes mellitus is due to either absolute deficiency of insulin (Type 1) or insulin resistance and reduced insulin secretion (Type 2). In both types metabolic disturbances of carbohydrates, proteins and lipids occur with serious long-term consequences including atheroma, micro-angiopathy (which can lead to blindness and kidney damage) and neuropathy. 

Sahin K, Onderci M, Tuzeu M, Ustundag B, Cikim G, Ozercan IH, Sriramoju V, Juturu V, Komorowski JR. Effect of chromium on carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus the fat-fed, streptozotocin-treated rat. Metabolism. 2007 56 1233 0. 

The clinical impact of insulin resistance ranges from subclinical hyperin-sulinemia to major life-limiting disturbances of carbohydrate and lipid metabolism [10-13]. The main clinical concern derives from the association between impaired insulin action and the development of vascular disease [14-17]. Microvascular disease is a complication of type 2 diabetes mellitus, in which insulin resistance is a prominent feature. Moreover, atherosclerotic macrovascular disease has a more complex association with insulin resistance that extends beyond hyperglycemia [18]. 

Maturity-onset diabetes (now more frequently termed Type II or non-insulin-dependent diabetes mellitus, NIDDM) is associated with obesity, hyperlipoproteinaemia and an increased risk of cardiovascular disease. Lipid metabolism tends to be enhanced and an important characteristic is... 

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