Diabetes mellitus

25 Diabetes mellitus




The stimulation of glucose uptake in peripheral tissue(e.g. skeletal muscle and adipose tissue) is an important function of insulin (see Fig. 1.12). The inability to regulate plasma glucose in the normal physiological range is central to diabetes mellitus, accounting for the hyperglycaemia, increase in thirst (polydipsia), increased glucose in urine (glycosuria) and large volumes of dilute urine (polyuria). High plasma glucose leadsto retinal disease, peripheral nerve dysfunction, atherosclerosis and peripheral vascular disease. Type I diabetes is an autoimmune disease that leads to the destruction of pancreatic beta cells in the young. In contrast, type II diabetes affects adults and has a number of predisposing factors, including genetics, obesity and sedentary lifestyle. It is also characterized by impaired insulin secretion from pancreatic beta cells coupled with an inability of peripheral cells to respond to insulin, commonly referred to as insulin resistance. The mechanism of this resistance include defects in glucose transport mechanism, glucotoxicity and lipotoxicity. The release of insulin from beta cells of the pancreas is regulated by plasma glucose (Figs 3.25.1 and 3.25.2) and a range of pharmacological agents can be used to reduce hyperglycaemia in diabetes mellitus (Fig. 3.25.3).






Insulin


Insulin is used to treat type I diabetes, reducing hepatic glucose production and improving glucose utilization by skeletal muscle. The biological activity of insulin is impaired by the gastrointestinal tract and it must, therefore, be given s.c., although in emergency it is administered i.v. There are many insulin formulations that slow absorption from the injection site, resulting in different times to reach peak insulin levels and duration of action (e.g. short-acting (e.g. regular, semilente), intermediate (e.g. lente, neutral protamine (isophane) insulin) and long-acting (ultralente) insulin). These allow the patient some flexibility in matching calorific intake with lifestyles. Regular insulin consists of crystalline zinc insulin that is injected 30 min before a meal, resulting in peak plasma levels of insulin within 2 to 3 h and an effect that lasts for 6 h. Insulin lispro and Insulin aspart are genetically engineered recombinant monomeric forms that do not dimerize and, therefore, are more rapidly absorbed; they are administered just prior to a meal. Because of their short duration of action, these monomeric analogues produce less hypoglycaemia than regular insulin. Intermediate preparations consist of large insulin crystals prepared in buffer or with addition of protamine in order to reduce solubility. Morphous zinc insulin and insulin zinc crystals in acetate buffer (lente) or insulin in a phosphate buffer together with protamine (NPH) allow insulin to dissolve more slowly from the site of injection, giving a more gradual onset (peak 6–10 h) and prolonged duration (20 h). Similarly, ultralente insulin consists of poorly soluble insulin zinc crystals that results in peak plasma levels within 20 h and a duration of 30 h. An important unwanted effect of insulin is hypoglycaemia, which can result in insufficient plasma glucose to meet the demands of the central nervous system, pontentially causing brain damage. Hypoglycaemia can be avoided by eating a sweet snack or drink or an infusion of glucose can be administered if the patient is unconscious.

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Jul 18, 2016 | Posted by in PHARMACY | Comments Off on Diabetes mellitus

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