Chronic diabetes complication retinopathy

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... 

The natural history of the disease is determined by the onset and extent of chronic diabetic complications. Microangiopathic changes are diabetes-specific, causing retinopathy, nephropathy and alterations in the peripheral and autonomous nervous system. Macroangiopathy, which is more typical for Type-II diabetes, leads predominantly to cardiovascular complications with coronary heart disease, myocardial infarction and peripheral vascular occlusion. 

The roots of S. oblonga have been extensively used for the treatment of diabetes in the Ayurvedic system of traditional Indian medicine. From the ethyl acetate soluble portion of the methanolic extract from the roots of S. oblonga Matsuda et al. isolated compound (14), a friedelane-type triterpene [42]. The methanolic extract and the ethyl acetate soluble portions were found to show inhibitory activity on aldose reductase, which is related to chronic diabetes complications such as peripheral neuropathy, retinopathy and cataracts. Compound (14) was assayed for aldose reductase rat lens inhibitory activity. It showed inhibition percentages of 21.8 % at a concentration of 30 pM and 48.2 % at a concentration of 100 pM. The activity of (14) and other terpenoids isolated from this plant could prove to be the reason for the popular use of the plant in the Ayurvedic system for the treatment of diabetes. 

Diabetes continues to be a major cause of excessive morbidity, severe disability and premature death in Western populations. In developed countries, the cost of diabetes to society may be estimated to be as high as 5% of the total health costs, much of which relates to the chronic vascular complications of this disorder (Williams, 1991). The vascular lesion in diabetes consists of (1) microangiopathy, distinguished by thickening of capillary basement membranes resulting in increased vascular permeability, which is clinically manifested as diabetic retinopathy (Fig. 12.1a) and/or nephropathy (Fig. 12.1b), and (2) macroangiopathy (Fig. 12.2),... 

In Ayurveda and folklore medicines, cinnamon is used in the treatment of diabetes. Cinnamon is reported to reduce the blood glucose level in non-insulin-dependent diabetics. Therapeutic studies have proved the potential of cinnamaldehyde as an antidiabetic agent. Cinnamaldehyde inhibits aldose reductase, a key enzyme involved in the polyol pathway. This enzyme catalyses the conversion of glucose to sorbitol in insulin-insensitive tissues in diabetic patients. This leads to accumulation of sorbitol in chronic complications of diabetes, such as cataract, neuropathy and retinopathy. Aldose-reductase inhibitors prevent conversion of glucose to sorbitol, thereby preventing several diabetic complications (Lee, 2002). 

The complication risk in Type-I diabetes is related not only to duration of the disease but also to the degree of glycaemic control, blood pressure and genetic susceptibility (Hanssen, 1991). The most frequent chronic complication in Type-I diabetes is diabetic background retinopathy, with a near-100% occurrence rate after 15 years diabetes duration. Manifestations of diabetes, however, can be found in all ocular structures (Table 1). 

Insulin therapy has been dramatically effective in eliminating keto-acidotic coma as a cause of death in diabetics. However, while prolonging life, insulin therapy does not prevent the occurrence of disabling complications of chronic diabetes, such as neuropathy, nephropathy, retinopathy and cataracts [ 13-Insulin therapy is only partially effective in normalizing glucose levels, and the occurrence of diabetic complications appears to be related to the severity and duration of diabetic hyperglycaemia. 

Patients with type 1 diabetes (previousiy caiied juveniie or insulin-dependent diabetes) have an absolute deficiency of insulin, which produces chronic hyperglycemia (elevated blood glucose) with elevated risk for ketoacidosis and a variety of long-term complications, including retinopathy, neuropathy, nephropathy, and cardiovascular complications. 

As noted previously, available therapies moderate the hyperglycemia of diabetes, but fail to completely normalize metabolism. The long-stand-hg elevation of blood glucose causes the chronic complications of diabetes—premature atherosclerosis, retinopathy, nephropathy, and neuropathy. Intensive treatment with insulin (see p. 339) delays the onset and slows the progression of these long-term complications. For example, the incidence of retinopathy decreases as control of blood glu-... 

A 27-year-old woman with diabetes mellitus, complicated by diabetic retinopathy and chronic renal insufficiency with anemia, developed methemoglobinemia (11%) after peribulbar blockade with prilocaine 80 mg, bupivacaine 30 mg, hyaluronidase, and napha-zoline (325). She recovered uneventfully after methylthioninium chloride 1.5 mg/kg. 

Patients with both type 1 and type 2 diabetes are at high risk for the development of chronic complications. Diabetes-specific microvascular pathology in tlie retina, renal glomerulus, and peripheral nerve produces retinopathy, nephropathy, and neuropathy. As a result of these microvascular complications, diabetes is the most frequent cause of new cases of bfindness in the industrialized world in persons between 25 and 74 years and the leading cause of end-stage renal disease.Diabetes is also associated with a marked increase in atherosclerotic macrovascular disease involving... 

Diabetes mellitus is a group of metabolic diseases characterized by an increased blood glucose level secondary to defects in insulin secretion and/or action. According to the American Diabetes Association, as of 2002, the United States diabetes prevalence is 18.2 million people (6.3% of the population). Diabetics suffer from acute complications of the disease such as diabetic ketoacidosis and hyperosmolar nonketotic syndrome as well as chronic complications ranging from microvascular disease (nephropathy, neuropathy, retinopathy) to macrovascular disease (1). 

Substituted spiro[imidazolidine-4,4 (T/0quinazoline]-2,2, 5(3 /0-triones (713) (Scheme 109) have been prepared and tested as aldose reductase inhibitors, which are of therapeutic interest in counteracting chronic complications of diabetes (retinopathy, neuropathy, nephropathy, cataracts). The spiro derivatives (713) were prepared from 1-carbamoylisatins (711) and S-ethylisothiouronium bromide with subsequent treatment of the 4-(2-ethyl-2-isothioureido)carbonyl-3,4-dihydro-4-hyd-roxy-2(l/f)quinazolinone (712) with acid <91CPB1694>. 

Protein giycation. Modest increases in the blood glucose concentration result in glucose reacting non-enzymically with the free amino groups of amino acid residues in cellular and extracellular proteins. They are associated with the development of the chronic complications associated with diabetes such as neuropathy, nephropathy and retinopathy (Chapter 28). 

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