Diabetes mellitus pathogenesis

Bays, H., Mandarino, L., and DeEronzo, R. A. (2004). Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus Peroxisomal proleferator-activated receptor agonists provide a rational therapeutic approach. /. Clin. Endocrinol. Metab. 89, 463 78. 

Akerblom, H.K., Knip, M., Hyoty, H., Rejijonen, H., Virtanen, S., Savilahti, E. and Ilonen, J. (1997). Interaction of genetic and environmental factors in the pathogenesis of insulin-dependent diabetes mellitus, Clinica Chimica Acta, 257, 143-156. 

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. 

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 pathogenesis of type I diabetes is autoimmune destruction of the cells of the pancreas. The factor or factors that trigger this autoimmune response are unknown. Predisposing factors appear to include certain major histocompatibility complex haplotypes and autoantibodies to various islet cell antigens. The progression of the autoimmune response is characterized by lymphocytic infiltration and destruction of the pancreatic cells resulting in insulin deficiency. Type I diabetes mellitus constitutes about 10% of cases of diabetes mellitus. 

Mandrup-Poulsen, T., Corbett, J. A., McDaniel, M. L., and Nerup, J. (1993). What are the types and cellular sources of free radicals in the pathogenesis of type 1 (insulin-dependent) diabetes mellitus Diabetologia 36, 470-471. 

The purpose of this chapter is to review the normal physiologic roles of the pancreatic hormones and to describe the pathogenesis and treatment of diabetes mellitus. Diabetes mellitus has many sequelae that influence patients neuromuscular and cardiovascular functioning. Patients with diabetes mellitus often undergo physical rehabilitation for problems related to the condition. Consequently, the nature of diabetes mellitus and the pharmacotherapeutic treatment of this disease are important to physical therapists and occupational therapists. 

Diabetes mellitus is apparently not a single, homogeneous disease but rather a disease existing in at least two primary forms.35 90 Patients with diabetes mellitus are usually classified as having either type 1 or type 2 diabetes, depending on the disease pathogenesis. The primary characteristics of type 1 and type 2 diabetes mellitus are summarized in Table 32-1. Specific aspects of these two primary forms of diabetes mellitus are discussed in more detail below. 

J. Y. and Stoffers, D. A. (2006) Role of glucagon-like peptide-1 in the pathogenesis and treatment of diabetes mellitus. hit J Biochem Cell Biol 38, 845-859. 

Thl proinflammatory cytokines such as IFN-y, IL-1/3, IL-12, and TNF-a released by macrophage and T lymphocytes in the vicinity of pancreatic beta cells have been implicated in the pathogenesis of type I (insulin-dependent) diabetes mellitus. Moreover, IL-18 serum levels are increased selectively during the early, subclinical stage of type I diabetes mellitus (N5). 

Eisenbarth GS Classification, diagnostic tests, and pathogenesis of Type I Diabetes Mellitus, in Becker KL (ed) Principles and Practice of Endocrinology and Metabolism. 3rd ed. Lippin-cott Williams and Wilkins, 2001, pp. 1307-1314. 

O Brien TD. Pathogenesis of feline diabetes mellitus. Mol Cell Endocrinol 2002 197(1-2) 213-9. 

Pathogenesis and complications (A). Type I diabetes mellitus typically manifests in childhood or adolescence (juvenile onset diabetes mellitus) it is caused by the destruction of insulin-producing B cells in the pancreas. A genetic predisposition together with a precipitating factor (viral infection) could start an autoimmune reaction against B-cells. Replacement of insulin (daily dose-40U, equivalent to -1.6 mg) becomes necessary. 

Y2. Yki-Jarvinen, H., Pathogenesis of non-insulin-dependent diabetes mellitus. Lancet 343,91-95 (1994). 

Militante JD, Lombardini JB, and Schaffer SW (2000) The role of taurine in the pathogenesis of the cardiomyopathy of insulin-dependent diabetes mellitus. Cardiovascular Research 46, 393 02. 

The pathogenesis of vincristine-induced neuropathy has not been fully elucidated, but very probably altered axoplasmic transport processes are of major importance, since neurons treated with vincristine lose portions of their axonal microtubules (35). There is marked interindividual variability in sensitivity to this toxic effect, partially based on different predisposing factors, for example diabetes mellitus, pretreatment with other potentially neurotoxic agents (such as cisplatin and taxanes), or familial disorders (such as Charcot-Marie-Tooth syndrome) (37,51,52). 

Recent researches have indicated that lipid peroxidation is involved in the pathogenesis of other human diseases such as hypoxic-ischemic reperfusion injury, cancers, Alzheimer s disease, rheumatoid arthritis, renal dysfunction, and diabetes mellitus. 

Obesity plays significant role in the pathogenesis of a number of physical conditions (Lawrence and Kopelman 2004). These include diabetes mellitus, hypertension, coronary heart disease, some forms of cancer, gall bladder disease, respiratory disease, and osteoarthritis. In addition, being obese can lead to profound psychological disturbances and can have a major impact on social relationships and employment prospects. 

Pathogenesis of Type 1 Diabetes Mellitus Type 1 diabetes mellitus results from a cellular-mediated autoimmune destruction of the insuhn-secreting cells of pancreatic p-cells. In the vast majority of patients, the destruction is mediated by T cells. This is termed type lA or immune-mediated diabetes (Box 25-2). The a-, 8-, and other islet cells are preserved. The islet cells have a chronic mononuclear cell infiltrate, called insulitis. The autoimmune process leading to type 1 diabetes begins months or years before the clinical presentation, and an 80% to 90% reduction in the volume of the j3-cells is required to induce symptomatic type 1 diabetes. The rate of islet cell destruction is variable and is usually more rapid in children than in adults. 

---