Diabetes, complications with

Usually these three biophysical mechanisms interact precisely to provide a highly efficient barrier against water loss and retain water within the tissue to maintain flexibility and catabolic activity. Nevertheless, this barrier is continually prone to perturbation by both external forces (UV, low RH, cold temperatures, and surfactants), and internal factors (cutaneous disease, psychological stress, and diabetic complications). With decreased performance of the water barrier the increased loss of water from the tissue ultimately leads to the formation of dry skin. 

The complex thioamide lolrestat (8) is an inhibitor of aldose reductase. This enzyme catalyzes the reduction of glucose to sorbitol. The enzyme is not very active, but in diabetic individuals where blood glucose levels can. spike to quite high levels in tissues where insulin is not required for glucose uptake (nerve, kidney, retina and lens) sorbitol is formed by the action of aldose reductase and contributes to diabetic complications very prominent among which are eye problems (diabetic retinopathy). Tolrestat is intended for oral administration to prevent this. One of its syntheses proceeds by conversion of 6-methoxy-5-(trifluoroniethyl)naphthalene-l-carboxyl-ic acid (6) to its acid chloride followed by carboxamide formation (7) with methyl N-methyl sarcosinate. Reaction of amide 7 with phosphorous pentasulfide produces the methyl ester thioamide which, on treatment with KOH, hydrolyzes to tolrestat (8) 2[. 

A relationship between polyol pathway activity and reduction in endothelium-dependent relaxation in aorta from chronic STZ-diabetic rats has recently been reported (Cameron and Cotter, 1992). In agreement with several previous studies (Oyama et al., 1986 Kamata et al., 1989), endothelial-dependent relaxation was defective in the diabetic rats but the deficit was prevented by prior treatment with an AR inhibitor. The mechanism underlying the defect has been speculated to be due to decreased production of endothelium-derived relaxing factor (EDRF) or nitric oxide, NO (Hattori et al., 1991). It has been speculated that these vascular abnormalities may lead to diminished blood flow in susceptible tissues and contribute to the development of some diabetic complications. NO is synthesized from the amino-acid L-arginine by a calcium-dependent NO synthase, which requires NADPH as a cofactor. Competition for NADPH from the polyol pathway would take place during times of sustained hyperglycaemia and... 

Aminoguanidine has been shown to prevent the formation of AGEs (Brownlee et al., 1986) and treatment with this drug prevents retinal pericyte loss in STZ-induced diabetic rats (Hammes et al., 1990). More recendy, functional and structural impairments in peripheral nerves are ameliorated by aminoguanidine in male Wistar rats (Yagihashi et al., 1992). These data surest that inhibitors of non-enzymatic glycosyiation may have a future role in the treatment of diabetic complications. 

N2. Nakata, H., Horita, K., and Eto, M., Alteration of lipoprotein(a) concentration with glycemic control in non-insulin-dependent diabetic subjects without diabetic complications. Metab., Clin. Exp. 42, 1323-1326 (1993). 

Rhetsinine (2), isolated from the hot water extract of Evodia rutae-carpa (family Rutaceae), was found to inhibit aldose reductase with an IC50 value of 24.1 /rM furthermore, the isolate inhibited sorbitol accumulation by 79.3% at 100 This compound could find potential use in the treatment of diabetic complications. Tetramethylpyrazine (3), one of the active components in Qing Huo Yi Hao, displayed strong antioxidant and endothelial protective effects, which can be comparable as Qing Huo Yi Hao this result indicated that some therapeutic potential of Qing Huo Yi Hao for vascular complications of diabetes may be attributed to the presence of tetramethylpyrazine (3). ... 

Wei J, Wu J, Jiang J, Wang S, Wang Z. (2004) Clinical study on improvement of type 2 diabetes mellitus complicated with fatty liver treatment by berberine. Zhong Xi Yi Jie He Ganbing Za Zhi 14 334-336. 

Hypersensitivity to sulfonylureas diabetes complicated by ketoacidosis, with or without coma sole therapy of type 1 (insulin-dependent) diabetes mellitus diabetes when complicated by pregnancy. 

Patients with both type 1 and type 2 diabetes are prone to complications. The specific chronic diabetic complications are due to microangiopathy and include neuropathy, retinopathy and nephropathy. Recent data stress the vital role of hyperglycaemia and oxidative stress in their pathophysiology. Premature atherosclerosis (which can be considered... 

Other complications arising from insuhn therapy are uncommon. Sometimes, diabetics treated with exoge-... 

Metformin works best in patients with significant hyperglycemia and is often considered first-line therapy in the treatment of mild to moderate type II overweight diabetics who demonstrate insulin resistance. The United Kingdom Prospective Diabetes Study demonstrated a marked reduction in cardiovascular comorbidities and diabetic complications in metformin-treated individuals. Metformin has also been used to treat hirsutism in individuals with polycystic ovarian syndrome and may enhance fertility in these women, perhaps by decreasing androgen levels and enhancing insulin sensitivity. 

Clinical trials of ARIs have yielded encouraging results in alleviating painful symptoms of diabetic complications. However, unacceptable side effects related to toxicity or inadequate pharmocokinetic profiles have rendered most of the drug candidates undesirable. Nevertheless, several ARIs are commercially available in some countries and more appear to be in the pipeline. The therapeutic rationale for treatment of human diabetics with ARIs to delay or prevent onset of diabetic complications is compelling. Animal models with experimentally induced hyperglycemia develop complications that are morphologically and functionally similar to that seen in the human diabetic patient. Many structurally... 

Klein J, Ott V, Schutt M, Klein HH. Recurrent hypoglycae-mic episodes in a patient with Type 2 diabetes under fibrate therapy. J Diabetes Complications 2002 16(3) 246-8. 

The closed-loop type artificial pancreas (specifically 8-cell), which consists of an automatic continuous monitor of blood glucose level (BGL) and an automatic injector of insulin which are coupled with feed-back system, has great potential for prevention of diabetic complication such as micro-angiopathies(l). A large-scale closed-loop type artificial pancreas for bedside use has already been developed and is clinically used at some laboratories and hospitals (2-4). However, this device is limited to only bedside use. On the other hand, the open-loop type artificial pancreas which consists of only a insulin injecting pump without an automatic continuous monitor of BGL, has been developed and is going to be clinically used(5-7). This system, however, can not completely control BGL as well as the bare pancreas in a normal body and often causes lower BGL(8-9). 

Inukai T, Inukai Y, Matsutomo R, et al. Clinical usefulness of doxazosin in patients with type 2 diabetes complicated by hypertension effects on glucose and lipid metabolism. J Int Med Res. 2004 32 2 06-213. 

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