Insulin Therapy and Hypoglycemia - Present and Future

Abstract

Over the last few decades the prevalence of diabetes has dramatically grown in most regions of the world. In 2010, 285 million people had diabetes and it is estimated that the number will increase to 438 million in 2030 (1). About 5-10% of them have type 1 diabetes. Both types of diabetes are characterized by a progressive decline of pancreatic beta cell function and mass. In type 1 diabetes, the chronic autoimmune process causes the selective destruction of insulin-producing beta cells by the auto-reactive T cells in genetically predisposed individuals. There is a continuous loss of functional C-peptide responses and at the time of clinical presentation the beta cell mass is reduced by 70–90 %, as suggested by anatomic studies (2, 3). This results in an inability to secrete sufficient amounts of insulin and loss of metabolic control. As a consequence, exogenous insulin replacement in the form of multiple subcutaneous injections or continuous subcutaneous insulin infusions (CSII) is essential for patients with type 1 diabetes. It prevents death from acute metabolic complications and assures normal growth and development, maintenance of normoglycemia and prevention of end-organ complications. Type 2 diabetes results from an entirely different pathophysiological process. It is characterized by an increased resistance to insulin action in the peripheral tissues with decreased glucose uptake and enhanced hepatic glucose output associated with impaired insulin-secretory capacity caused by a progressive decline of beta cell function over time. Studies indicate a substantial loss of beta cell mass (of about 25-60 %) by the time of diagnosis, mainly secondary to increased apoptosis and impaired augmentation of cell mass through neogenesis (4, 5). The clinical onset is due to the reduction of beta cell mass per se and to a concomitant dysfunction of residual beta cells (6, 7). The beta cell failure, which seems to occur much earlier during the natural history of the disease than previously thought, results in significant insulin deficiency and by then, insulin administration is required in order to achieve glycemic control (8, 9).