Intensive treatment of type 1 diabetes

The evolution of the treatment of type 1 diabetes mellitus in the twentieth century has been extraordinary. Treatment strategies before the availability of animal insulin preparations in 1922 were unsuccessful, and survival was measured in weeks. The discovery of insulin was one of the most important contributions in the history of medicine, yet new problems developed. The initial insulin injections were administered intramuscularly and often produced a painful abscess. 17 Individuals with type 1 diabetes, instead of succumbing to diabetic ketoacidosis, now developed microvascular disease, neuropathy, and premature macrovascular disease resulting in enormous morbidity and premature mortality. During the decades after the discovery of insulin, most of the advances in the treatment of type 1 diabetes were related to the improvement of the insulins (mostly related to impurities) and the addition of different insulin preparations, which prolonged their duration of action. Some would suggest, however, that the introduction of longer-acting insulin preparations actually retarded the progress of type 1 diabetes therapy. 78 These longer-acting insulins were developed to improve patient convenience because the initial soluble (regular) insulin required multiple injections to limit severe hyperglycemia and ketosis. Contemporary diabetes management began to take form in the late 1970s and early 1980s with the introduction of several new tools. First was the use of self-monitoring of blood glucose (SMBG), replacing the messy and often less helpful urine testing. 115,118 For the first time, insulin dose or food intake could be adjusted on the basis of the blood glucose level measured outside the hospital setting. At the same time, physicians and their patients were able to assess diabetes control objectively with glycated hemoglobin levels. 57,93 Although useful in routine clinical management, 56 this test also allowed researchers both to create and to describe populations for clinical trials that required precise evaluation of diabetes control. Strategies to provide more physiologic insulin replacement were also developed. 107 Attempts to mimic the normal β cell were far from perfect. All regimens of subcutaneous insulin require a massive bolus of insulin, as opposed to the normal (and much smaller by comparison) pulsatile secretion of insulin into the portal circulation. It is therefore not surprising that hypoglycemia is the limiting factor in the treatment of type 1 diabetes. For example, with exercise, hypoglycemia is normally prevented both by a decrease in circulating insulin and an increase in glucagon and epinephrine. For individuals with type 1 diabetes, any change in the enormous insulin doses for exercise must be based on a guess, and abnormal glucagon and epinephrine counterregulation is the rule, especially with long-standing disease. 9 Insulin replacement strategies for the 1980s 107 and even more so for the 1990s 65,114 stressed the importance of smaller doses of insulin spread out throughout the day, with the flexibility to change insulin dose as needed to correct hyperglycemia, supplement for additional anticipated carbohydrate, or subtract for exercise. Although significant effort is required, it has become theoretically possible to maintain near-normal glycemia in the majority of patients with type 1 diabetes. The announcement of the Diabetes Control and Complications Trial (DCCT) in 1993 dramatically resolved any controversy that meticulous glycemic control is possible and that it reduces microvascular complications in type 1 diabetes. 128 The relationship between glycemic control and microvascular complications has been confirmed in other studies. 81,95,103 This article reviews current strategies for the treatment of type 1 diabetes. The introduction of a variety of new tools over the past two decades has provided unique opportunities for meticulous glycemic control. This variety has also resulted in the evolution of complex treatment programs, at least when compared with the relatively simple therapies for type 1 diabetes in the past.