Abstract
Total pancreatectomized patients has similar pathophysiological aspects with insulin-dependent diabetes mellitus (IDDM) in absolute insulin deficiency, both hepatic and peripheral insulin resistance, and, the development of diabetic micro—as well as macroangiopathy due to long-term hyperglycemia. Glucagon deficiency in pancreatectomized patients, however, causes more frequent hypoglycemia due to delayed hepatic glucose production and less insulin requirement than in IDDM patients. The optimal insulin therapy for these pancreatectomized patients is discussed from the viewpoint of drug delivery system (DDS). 1. Targeting : The study of hepatic and peripheral glucose handling in pancreatectomized diabetic dogs revealed that intraportal insulin administration results in a smaller gain in hepatic glucose handling than peripheral insulin administration. This means the superiority of intraportal insulin delivery which appears to be safer and more suitable for attaining stable glycemic control in these patients. 2. Controlled-release : Closed-loop insulin infusion system is optimal especially for postprandial glycemic regulation in these patients because of unstable enteric nutritional absorption, whereas it is still not available due to the lack of glucose sensor for long-term clinical usage. Therefore, frequent insulin dose adjustment based on self-monitoring of blood glucose (SMSG) is the second best. 3. The necessity of safer intraportal indweling cannula for long-term clinical usage : Intraportal cannulation may provoke portal thrombosis as well as infectious disease. These problems in biocompatibility promoted intraperitoneal delivery in stead. From these viewpoints, ultimate goal of future therapy for diabetes mellitus is discussed.
