Type 2 diabetes mellitus -induced

Knockout mice have been reported for several FATPs [1]. As insulin desensitization has been closely linked to excessive fatty acid uptake and intracellular diacylgly-cerol and TG accumulation, these animal models were particularly evaluated in the context of protection from diet-induced type 2 diabetes ( Type 2 Diabetes Mellitus (T2DM)). In addition, studies on human subjects have also established genetic links between polymorphisms in FATP genes and metabolic alterations [1]. 

It has been proposed that the development of the complications of diabetes mellitus may be linked to oxidative stress and therefore might be attenuated by antioxidants such as vitamin E. Furthermore, it is discussed that glucose-induced vascular dysfunction in diabetes can be reduced by vitamin E treatment due to the inactivation of PKC. Cardiovascular complications are among the leading causes of death in diabetics. In addition, a postulated protective effect of vitamin E (antioxidants) on fasting plasma glucose in type 2 diabetic patients is also mentioned but could not be confirmed in a recently published triple-blind, placebo-controlled clinical trial [3]. To our knowledge, up to now no clinical intervention trials have tested directly whether vitamin E can ameliorate the complication of diabetes. 

Araya, A.V. et al., Ex vivo lipopolysaccharide (LPS)-induced TNF-alpha, IL-lbeta, IL-6 and PGE2 secretion in whole blood from type 1 diabetes mellitus patients with or without aggressive periodontitis, Eur. Cytokine Netw., 14, 128, 2003. 

Clark, C. A., Gardiner, J., McBurney, M. 1., Anderson, S., Weatherspoon, L. J., Henry, D. N., and Hord, N. G. (2006). Effects of breakfast meal composition on second meal metabolic responses in adults with type 2 diabetes mellitus. Eur. J. Clin. Nutr. 60,1122-1129. Cohen, L. A., Zhao, Z., Zang, E. A., Wyrm, T. T., Simi, B., and Rivenson, A. (1996). Wheat bran and psyllium diets Effects on N-methylnitrosourea-induced mammary tumorigenesis in F344 rats. /. Natl. Cancer Inst. 88, 899-907. 

Burge MR, Schmitz-Fiorentino K, Fischette C, Qualls CR, Schade DS. A prospective trial of risk factors for sulfonylurea-induced hypoglycemia in type 2 diabetes mellitus. JAMA I998 279(2) l 37 13. 

Saule H. Insulin-induzierte Odeme bei Adoleszenten mit Diabetes mellitus Typ I. [Insulin-induced edema in adolescents with type 1 diabetes mellitus.] Dtsch Med Wochenschr 1991 II6(3I-32) II9I 1. 

Reynolds RM, Walker JD. Hypoglycaemia induced by disopyramide in a patient with Type 2 diabetes mellitus. Diabet Med 2001 18(12) 1009-10. 

Insulin-dependent diabetes mellitus (IDDM) is an example of a metabolic disease under active consideration for inducible gene therapy strategies. In this disorder, inflammatory cytokines have been shown to activate apoptosis in pancreatic beta cells. Experimental studies indicate that expression of insulinlike growth factor-1 (IGF-1) can prevent the cytokine-mediated destruction of beta cells of the pancreas (Giannoukakis et al., 2001). Regulated expression of IGF-1 in human pancreatic islets, to preserve beta cell function, may be a useful approach in the treatment of certain types of diabetes (Demeterco and Levine, 2001). 

Noninsulin-dependent (type 2) diabetes is the prevalent form of diabetes mellitus found in populations chronically exposed to inorganic arsenic from the environment (Rahman et al, 1998 Tseng, 2002). Type 2 diabetes is characterized by insulin resistance of internal organs and peripheral tissues that results in impaired glucose utilization, and, consequently, in abnormally high blood glucose levels between and especially after meals. Insulin resistance and P-cell dysfunction can be induced by chronic arsenic exposure and these defects may be responsible for arsenic-induced diabetes mellitus (Tseng, 2004). 

A 65-year-old woman with type 2 diabetes mellitus and coronary artery disease received a 0.25 mg/kg bolus of abciximab at the time of intervention followed by an infusion of 10 micrograms/minute for 12 hours. Her baseline platelet counts were 286 x 10 /1 before use, 385 X 10 /1 at 2 hours, and 296 x 10 /1 at 18 hours. On day 7 she developed petechiae over her legs and her platelet count was 1 x 10 /1. Coagulation tests were normal and there was no evidence of heparin-induced thrombocytopenia. She received 10 units of single-donor platelets and recovered slowly over the next 4 days. The platelet count was 114 x 10 /1 on day 12. 

The exact mechanisms of tacrolimus-induced diabetes are unknown. In one renal transplant patient with genetic susceptibility, tacrolimus was associated with insulin-dependent diabetes mellitus and the simultaneous occurrence of anti-glutamic acid decarboxylase antibody (54). Within 2 months after conversion from tacrolimus to ciclosporin, the antibody was no longer detected and the patient s insulin requirements fell dramatically. Tacrolimus-induced direct beta cell toxicity, with subsequent development of beta cell autoimmunity, was therefore suggested as a possible mechanism in patients with genetic susceptibility for type I diabetes. 

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. 

The influence of antioxidants (e.g. vitamin E or a-tocopherol, vitamin C or ascorbic acid, and carotenoids, including P-carotene and lycopene) on autoimmune diseases has not been extensively studied. There is some evidence that damage induced by reactive oxygen species contributes to the destruction of pancreatic beta cells, brain tissue, and joints seen in diabetes mellitus type 1, multiple sclerosis, and rheumatoid arthritis, respectively. However, there are few prospective studies of antioxidant intake and risk of autoimmune diseases. Although there is some evidence of a reduced risk of rheumatoid arthritis and lupus with higher intake or serum levels of antioxidants, there are inconsistent findings with respect to which antioxidants or foods are involved (Comstock et al., 1997 Knekt et al., 2000 Cerhan et al., 2003). Only one prospective study of antioxidants and risk of multiple sclerosis is available, and that study reported no association with intakes of vitamin C, vitamin E, or carotenoids (Zhang et al., 2001). 

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