Pramlintide for diabetes mellitus

Description of the condition: The World Health Organisation defines diabetes mellitus as a metabolic disorder characterised by chronic hyperglycaemia with disturbances of carbohydrate, fat, and protein metabolism resulting from defects in insulin secretion, insulin action or both. The effects of diabetes mellitus include long-term damage, dysfunction and failure of various organs (WHO 1998). Of the major aetiological forms of diabetes mellitus, type 1 and type 2 diabetes account for the majority of cases. In both type 1 and type 2 diabetes there is a decline in the secretory function of pancreatic beta-cells. In type 1 diabetes the decline in insulin secretion to an absolute deficit of insulin is usually rapid and it is due to an autoimmune process or, less frequently, to unknown, idiopathic destruction of pancreatic beta-cells. In type 2 diabetes mellitus two processes coexist and interact over the course of the disease: insulin resistance - that is a diminished effect of insulin - and insulin deficiency (Kahn 2003). Insulin resistance in type 2 diabetes is frequently related to overweight and obesity. In type 2 diabetes insulin secretion failure is usually slow compared to type 1 diabetes with a progressive loss of beta-cells function and beta-cells mass due to yet unknown causes, other than autoimmunity but eventually determining the need for exogenous insulin administration to correct chronic hyperglycaemia (Weir 2004). Since the discovery of insulin made survival in diabetes possible accumulating epidemiological evidence demonstrated the causal relationship between hyperglycaemia and diabetes specific complications like retinopathy with the potential evolution to blindness, nephropathy potentially leading to end-stage renal failure and neuropathy. The effect of treating hyperglycaemia in preventing the development and progression of diabetes complications was convincingly demonstrated by two landmark trials - the DCCT in type 1 diabetes (DCCT 1993) and the UKPDS in type 2 diabetes (UKPDS 1998)